Robert Perlman

Robert Perlman
University of Chicago | UC · Department of Pediatrics

About

177
Publications
4,181
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
8,184
Citations
Citations since 2017
3 Research Items
764 Citations
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
Introduction
Additional affiliations
January 1987 - December 2011
University of Chicago
July 1981 - December 1996
University of Illinois at Chicago
Position
  • Head of Faculty
July 1971 - June 1981
Harvard Medical School
Position
  • Professor (Associate)

Publications

Publications (177)
Chapter
Archibald Garrod (1857–1936) is best remembered for introducing Mendelian inheritance into medicine and for his book, “Inborn Errors of Metabolism.” Garrod appreciated that inborn errors were products of our evolutionary history. The recognition of inborn errors led Garrod to the broader concept of chemical individuality. Chemical individuality, wh...
Article
Full-text available
The use of mice as model organisms to study human biology is predicated on the genetic and physiological similarities between the species. Nonetheless, mice and humans have evolved in and become adapted to different environments and so, despite their phylogenetic relatedness, they have become very different organisms. Mice often respond to experime...
Article
Full-text available
Archibald E. Garrod: the father of precision medicine Robert L. Perlman, MD, PhD1 and Diddahally R. Govindaraju, PhD In his 2015 State of the Union address, President Obama launched the Precision Medicine Initiative (PMI). In brief, the goal of this ambitious initiative is to improve health by tailoring the prevention and treatment of disease to g...
Article
Richard Landau, the longtime editor of Perspectives in Biology and Medicine, died on November 3, 2015. Richard grew up in St. Louis. Like many people of his generation, he was inspired to become a physician by Paul de Kruif ’s book Microbe Hunters (1926). Richard went to college and medical school at Washington University in St. Louis and came to t...
Article
Full-text available
Article
Evolutionary medicine is a new field whose goal is to incorporate an evolutionary perspective into medical education, research, and practice. Evolutionary biologists and physicians have traditionally been concerned with different problems and have developed different ways of approaching and understanding biological phenomena. Evolutionary biologist...
Book
Evolutionary concepts help explain why we remain vulnerable to disease, how pathogens and cancer cells evolve, and how the diseases that affected our evolutionary ancestors have shaped our biology. Evolution and Medicine interweaves the presentation of evolutionary concepts with examples that illustrate how these concepts enhance our understanding...
Article
Full-text available
Evolutionary biology was a poorly developed discipline at the time of the Flexner Report and was not included in Flexner's recommendations for premedical or medical education. Since that time, however, the value of an evolutionary approach to medicine has become increasingly recognized. There are several ways in which an evolutionary perspective ca...
Article
Morton Arnsdorf, the book review editor of Perspectives in Biology and Medicine, was tragically killed in an automobile accident on June 9, 2010. Mort grew up in Chicago, went to college at Harvard, and then to medical school at the Columbia University College of Physicians and Surgeons. In college, Mort majored in History of Science, and he retain...
Article
This lovely book comprises about 80 excerpts from the writings of 20th-century scientists, selected and introduced by Richard Dawkins. As Dawkins explains the purpose of the anthology: Our ability to understand the universe and our position in it is one of the glories of the human species. Our ability to link mind to mind by language, and especiall...
Article
Full-text available
New applications of evolutionary biology in medicine are being discovered at an accelerating rate, but few physicians have sufficient educational background to utilize them fully. This article summarizes suggestions from several groups who have considered how evolutionary biology can be useful in medicine, what physicians should learn about it, and...
Article
Full-text available
New applications of evolutionary biology in medicine are being discovered at an accelerating rate, but few physicians have sufficient educational background to use them fully. This article summarizes suggestions from several groups that have considered how evolutionary biology can be useful in medicine, what physicians should learn about it, and wh...
Article
One hundred and fifty years after the publication of On the Origin of Species, evolutionary biology has matured into an active, rigorous, and exciting field of scientific research. Evolution: The First Four Billion Years provides a wonderful introduction to this field. The book offers in-depth articles on the current state of our understanding of e...
Article
Logan Clendening’s Source Book of Medical History (1942) and Ralph Major’s Classic Descriptions of Disease (1945) have long served as invaluable references for medical students and physicians who were interested in the history of their profession. Until now, however, there has not been a comparable resource for students and practitioners of public...
Article
Full-text available
The populations of pathogens in individual hosts have many of the characteristics of multicellular organisms, or individuals. These populations go through a life cycle within a host and they reproduce by founding daughter populations in new hosts. Natural selection shapes the life history characteristics of pathogen populations--life expectancy, tr...
Article
In lieu of an abstract, here is a brief excerpt of the content: First, truth in labeling. The Plausibility of Life: Resolving Darwin's Dilemma is not about the plausibility of life. It is about the evolution of animal life, and especially about the origin of novelty in animal evolution. The central question that the book seeks to answer is, "How c...
Article
Abstract— Suspensions of isolated adrenal cells were prepared by digesting hamster adrenal glands with collagenase, and the secretion of catecholamine from these cells was studied. Acetylcholine (ACh) produces a dose-dependent increase in catecholamine secretion; half-maximal secretion is produced by 3 μm-ACh, and maximal secretion by 100 μm-ACh. T...
Article
Abstract– The uptake of 45Ca2+ into cell suspensions prepared from a transplantable rat pheochromocytoma was measured. The uptake of Ca2+ into these cells is biphasic; there is a rapid, initial uptake of Ca+, followed by a slower uptake that proceeds at a linear rate for at least 10min at 37°C. The uptake of Ca2+ is a linear function of the externa...
Article
Perspectives in Biology and Medicine 49.2 (2006) 311-313 The Epistemology of Development, Evolution, and Genetics contains 11 essays by Richard Burian, a philosopher and historian of biology at Virginia Polytechnic Institute and State University. Burian recognizes that the philosophy of biology, like philosophy generally, "should begin with wonder...
Article
Although natural selection might be expected to reduce the incidence and severity of disease, disease persists. Natural selection leads to increases in the mean fitness of populations and so will reduce the frequency of disease-associated alleles, but other evolutionary processes, such as mutation and gene flow, may introduce or increase the freque...
Article
Full-text available
Racial disparities in health care and health outcomes are a disturbing feature of the American health care system. Efforts to reduce or ameliorate these disparities must be informed by an understanding of the factors that underlie and contribute to them. The papers in this issue are based on a recent conference that was held at the University of Ch...
Article
Perspectives in Biology and Medicine 47.4 (2004) 475 The papers in this special issue of Perspectives in Biology and Medicine deal with the development of clinical research in the last half century as a basis for understanding the successes and current problems of the clinical research enterprise in the United States. In 1979, this journal publishe...
Article
We believe that support for academic clinical research has greatly declined in recent decades. Here we discuss our views on why this has happened. We define clinical or patient-oriented research as limited to the study of human beings or populations of individuals, and argue that its eclipse in favor of basic and "translational" research is the res...
Article
Perspectives in Biology and Medicine 45.1 (2002) 125-130 Publication -- typically publication of articles in peer-reviewed journals -- is part and parcel of the scientific process. Designing and carrying out experiments, and collecting and analyzing data, can be personally satisfying, if not exhilarating. Nonetheless, until the results of research...
Article
Perspectives in Biology and Medicine 45.1 (2002) 156 Van Rensselaer Potter, professor emeritus of oncology at the University of Wisconsin and a longtime member of our editorial board, died on 6 September 2001. After a distinguished career in cancer research,Van became interested in global issues of human health and environmental protection. In 1970...
Article
Perspectives in Biology and Medicine 44.2 (2001) 159-161 This issue of Perspectives in Biology and Medicine contains 10 papers from the Asilomar Symposium on Science, Ethics, and Society, which was held in February 2000 at the conference site in California that has become eponymous for the discussion of scientific policy issues. Twenty-five years e...
Article
The growth of physiology in the 19th and 20th centuries was accompanied by the development of disciplinary boundaries between physiology and other biological sciences. Physiology became the study of the mechanisms that underlie the functions of organisms and their component parts. Concern with the internal workings of organisms has led physiologist...
Article
Full-text available
The effects of pituitary and extrapituitary prolactin include cellular proliferation and differentiation. PC12 cells was used as a model to delineate respective signaling of prolactin. Prolactin acted as a mitogen for undifferentiated PC12 cells, as measured by significant increases in bromodeoxyuridine incorporation and in cell numbers, with an ef...
Article
Perspectives in Biology and Medicine 43.3 (2000) 460 James V. Neel, professor emeritus of human genetics and internal medicine at the University of Michigan, died on February 1, 2000. Dr. Neel was a founding member of our editorial board and a strong supporter of the journal. Among his many contributions to human genetics was the "thrifty gene" hyp...
Article
Chromaffin cells were isolated from bovine adrenal glands and fractionated into two distinct subpopulations by density gradient centrifugation on Percoll. Cells in the more dense fraction stored epinephrine (E) as their predominant catecholamine (81% of total catecholamines), contained high levels of phenylethanolamine N-methyltransferase (PNMT) ac...
Article
Several constituents of chromaffin granules were quantitatively determined in noradrenaline and adrenaline cells purified from bovine adrenal medulla. As far as secretory peptides are concerned noradrenaline granules contained slightly more secretogranin II, but much less chromogranin A than adrenaline granules. This can be explained by the depende...
Article
The effects of noradrenaline and other adrenergic agonists on lymphocyte activation were studied. Spleen and thymus cells from BALB/c mice were stimulated by mitogens and lymphocyte activation was monitored by measuring the incorporation of [methyl-3H]thymidine into DNA. Noradrenaline, adrenaline, isoproterenol and dopamine all inhibited the activa...
Article
Full-text available
We have previously shown that, as a consequence of low-dose melphalan (L-phenylalanine mustard (L-PAM) therapy, the hitherto immunosuppressed spleen cells from BALB/c mice bearing a large MOPC-315 tumor (in contrast to spleen cells from normal mice) acquire the ability to generate a greatly enhanced anti-MOPC-315 cytotoxic T lymphocyte (CTL) respon...
Article
The synthetic glucocorticoid dexamethasone enhanced histamine-evoked catecholamine secretion from cultured bovine chromaffin cells. Dexamethasone enhanced the effects of histamine on both adrenergic (epinephrine-rich) and noradrenergic (norepinephrine-rich) chromaffin cells but had a more dramatic effect on noradrenergic cells. Histamine-evoked sec...
Article
Our laboratory recently reported that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] rapidly increases the breakdown of membrane phosphoinositides, raises intracellular calcium concentration ([Ca2+]i), and translocates protein kinase C (PKC) from the cytosolic to the particulate fraction of Caco-2 cells. In the present experiments, we found that Caco-2 cel...
Article
1 The effects of tetraethylammonium chloride (TEA) on catecholamine secretion from primary cultures of noradrenaline-rich (noradrenergic) and adrenaline-rich (adrenergic) bovine chromaffin cells were studied. TEA stimulated catecholamine secretion from both cell types but was a much more effective secretory stimulus for noradrenergic cells. 2 TEA-i...
Article
Chromaffin cells have H1 histamine receptors. Histamine, acting at these receptors, increases the metabolism of inositol-containing phospholipids and stimulates catecholamine secretion from chromaffin cells. We have investigated the effects of histamine and other agents on the accumulation of inositol monophosphate (InsP1) and catecholamine secreti...
Article
Bovine chromaffin cells contain a family of renaturable protein kinases. One of these, a 60,000 M(r) kinase (PK60) that phosphorylated myelin basic protein in vitro, was activated fourfold when cells were treated with the protein kinase inhibitor staurosporine. Because staurosporine inhibits protein kinase C, the role of this kinase in the regulati...
Article
Pheochromocytomas that are usually noradrenergic arise commonly in the adult rat adrenal medulla. The widely studied PC12 cell line, that is representative of these rat adrenal tumors, is also noradrenergic. The reasons for the absence of epinephrine production by most rat pheochromocytoma cells are unknown, and there are currently no adrenergic ad...
Article
In recent years, much interest has centered on the commonalities and bi-directional interactions between the nervous system and the immune system. This review focuses on mechanisms through which, catecholamines, a class of neuro-endocrine molecules, modulate immune functions. Catecholamines can be immune suppressive and inhibit lymphocyte activatio...
Article
Treatment of bovine chromaffin cells with nicotinic agonists, phorbol esters, and growth factors increases protein kinase activity toward microtubule-associated protein-2 and myelin basic protein (MBP) in vitro. To characterize the kinases that are activated by these agents, we separated chromaffin cell proteins by electrophoresis in sodium dodecyl...
Article
BOVINE chromaffin cells have two components of whole-cell Ca2+ current: 'standard' Ca2+ currents that are activated by brief depolarizations, and 'facilitation' Ca2+ currents, which are normally quiescent but can be activated by large pre-depolarizations or by repetitive depolarizations to physiological potentials1-5. The activation of protein kina...
Article
Natural infection by mouse hepatitis virus (MHV) can affect interpretation of immunological studies in mice. MHV, a collective term describing a group of corona viruses, is found in natural infections in over 70% of laboratory mouse populations in the U.S.A. and Canada. Natural outbreaks of MHV in our animal colony afforded us the opportunity to st...
Article
Differential secretion of norepinephrine and epinephrine was studied in cultured bovine chromaffin cells. Nicotinic agonists and 55 mM K+ evoked a slightly greater release of norepinephrine than of epinephrine: The percentage of norepinephrine secreted was 1.5 to two times greater than the percentage of epinephrine secreted. In contrast, when the c...
Article
Previous studies have identified two components of whole-cell Ca2+ current in bovine chromaffin cells. The "standard" component was activated by single depolarizations, while "facilitation" could be activated by large prepulses or repetitive depolarizations. Neither current component was sensitive to changes in holding potential between -100 and -5...
Article
Full-text available
1. Cell-attached patch recordings from bovine chromaffin cells were performed with 90 mM-Ba2+ in the patch pipette and with isotonic potassium aspartate in the bathing solution to zero the membrane potential. Three different types of unitary Ca2+ channel activity could be distinguished in these recordings. 2. A 27 pS Ca2+ channel was distinguished...
Article
Treatment of bovine chromaffin cells with insulin-like growth factor-I (IGF-I) caused the activation of a protein kinase that phosphorylates microtubule-associated protein-2 (MAP-2) in vitro. Activation of MAP-2 kinase by IGF-I varied with the time of treatment (maximal at 10-15 min) and the concentration of IGF-I (maximal at 10 nM). The IGF-I-acti...
Article
Previous studies have shown that insulin-like growth factor-I (IGF-I) enhances secretagogue-stimulated Ca2+ uptake and catecholamine release in bovine chromaffin cells. This report describes the effect of IGF-I on the activity of tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2), the major regulatory enzyme in the pathway of catecholami...
Article
1. Antiphosphotyrosine antibodies were used to detect phosphotyrosine-containing proteins in immunoblots of bovine chromaffin cell proteins. 2. Unstimulated cells exhibited two major phosphotyrosine-containing proteins, which hadM r 's of 121,000 and 70,000. Insulin-like growth factor I (IGF-I) had little effect on the phosphotyrosine content of t...
Article
Whole-cell Ca2+ currents in cultured bovine chromaffin cells were studied using patch-clamp electrophysiology. With Ba2+ or Ca2+ as the current carriers, two separate components of whole-cell current could be distinguished by biophysical and pharmacological criteria. These components of Ca2+ current were different from T- or N-type Ca2+ channels pr...
Article
Facilitation calcium channels in unstimulated bovine chromaffin cells are normally quiescent but are activated by large pre-depolarizations or by repetitive depolarization in the physiological range. The activation of these 27-pS dihydropyridine-sensitive channels by repetitive stimulation, such as by increased splanchnic nerve activity, can lead t...
Article
The structurally similar compounds staurosporine and K252a are potent inhibitors of protein kinases. K252a has previously been reported to inhibit most or all of the effects of nerve growth factor (NGF) on PC12 pheochromocytoma cells, and staurosporine has been reported both to inhibit and to mimic NGF-induced neurite outgrowth from a PC12 cell sub...
Article
Abstract Previous studies have reported the presence of binding sites for insulin-like growth factor I (IGF-I) in membranes prepared from isolated bovine adrenal medullary cells, and IGF-I was found to regulate the secretory function of bovine chromaffin cells. In the present study, binding sites for IGF-I have been localized in sections of bovine...
Article
Chromaffin cells cultured in serum-free medium secreted a smaller percentage of their catecholamine stores in response to stimulation by high K+ (55 mM) than did cells cultured in serum-containing medium. Addition of insulin-like growth factor-I (IGF-I) to serum-free medium restored high K(+)-stimulated catecholamine secretion to the levels seen in...
Article
: Competitive binding studies indicated that PC 12 cells have receptors for insulin-like growth factor-I (IGF-I). There are ∼ 11,100 ± 1,500 IGF-I receptors/cell; these receptors have an apparent KD for IGF-I of 7.2 ± 0.6 nM. Covalent cross-linking of l25I-IGF-I to PC 12 cells labeled a 125,000-130,000-Mr protein, presumably the α-subunit of the IG...
Article
In order to study the role of protein kinase C in the regulation of tyrosine hydroxylase phosphorylation in PC12 cells, the effects of various agonists on diacylglycerol accumulation in PC12 cells were measured and the ability of these agonists to increase the phosphorylation tyrosine hydroxylase in protein kinase C-deficient cells was evaluated. B...
Chapter
In 1966, Levi-Montalcini and her colleagues reported that insulin stimulates RNA and lipid synthesis in sensory ganglia (Angeletti et al., 1966). Because these workers used high concentrations of insulin in their studies, the significance of their observations was not clear. The subsequent discovery of insulin-like growth factors (IGFs) and IGF rec...
Article
The binding of 125I-insulin-like growth factor-I (125I-IGF-I) to bovine chromaffin cells was measured. Chromaffin cell cultures contained 111,000 ± 40,000 IGF-I binding sites/cell. These sites bound IGF-I with a KD of 1.1 ± 0.3 nM and had a much lower affinity for insulin. Cross-linking studies showed that 125I-IGF-I bound to a protein that had an...
Article
The effects of insulin and insulin-like growth factors (IGFs) on the replication of PC12 pheochromocytoma cells were investigated. Incubation of PC12 cells for 2-3 days in low (0.3%) serum medium decreased [3H]thymidine incorporation into PC12 cell DNA to approximately 30% of that in control (15% serum) medium. Incubation of the cells in low serum...
Article
Elongation factor 2 (EF-2) and its associated kinase, Ca2+/calmodulin-dependent protein kinase III, have recently been identified as a major protein phosphorylation system in mammalian tissues. We have measured the phosphorylation of EF-2 in 32P-labeled superior cervical ganglia. Phosphorylation of EF-2 was increased by preganglionic stimulation or...
Article
1. 32P-Labeled proteins from the superior cervical ganglion of the rat were separated by two-dimensional gel electrophoresis and visualized by autoradiography. 2. The most heavily labeled phosphoprotein in the ganglion had a relative molecular weight of 83,000 and a pI of 4.5. Phosphorylation of this protein was increased by phorbol 12,13-dibutyrat...
Article
Electrical stimulation of the preganglionic cervical sympathetic trunk increases the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion of the rat by a nicotinic mechanism and by a noncholinergic mechanism. We have measured the incorporation of [32P]Pi into specific tryptic phosphopeptides in tyrosine hydroxylase in order to...
Article
Muscarine stimulates the hydrolysis of inositol-containing phospholipids and increases the activity of tyrosine hydroxylase in the ganglion. Vasopressin also stimulates the hydrolysis of inositol-containing phospholipids in the ganglion but does not increase the activity of tyrosine hydroxylase (tyrosine 3-monooxygenase) in this tissue. Most of the...
Article
PC12 cells are a clonal cell line derived from a rat pheochromocytoma. These cells are widely used as models for both adrenal chromaffin cells and sympathetic neurons. When PC 12 cells are grown in the absence of nerve growth factor (NGF), they appear as small, round, undifferentiated cells. In the presence of NGF, the cells stop dividing, enlarge,...
Chapter
Our laboratory has been interested in the mechanisms by which neuronal activity regulates neuronal metabolism. Specifically, we have been studying the mechanisms by which neuronal activity regulates tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2) activity and catecholamine synthesis in the superior cervical ganglion (SCG). The SCG is...
Book
This Festschrift volume in honor of Professor Alexander Karczmar is the outcome of a three-day symposium entitled "Neurobiology of Acetylcholine" held at Loyola University Medical Center from June 3 to 5, 1985. This volume serves two purposes. It expresses the respect and admiration of the contributors to Alex Karczmar, and it provides a forum for...
Article
Both muscarine and vasopressin have been shown previously to increase the accumulation [3H]inositol phosphates in superior cervical ganglia in which the phospholipids were labeled with [3H] inositol. In this study, we have compared the effects of muscarine and of vasopressin on phospholipid metabolism in the ganglion. The effects of these agents on...
Article
Phorbol 12,13-dibutyrate (PDBu) increased the production of 3,4-dihydroxyphenylalanine (DOPA) in the superior cervical ganglion of the rat. This effect occurred without a detectable lag and persisted for at least 90 min of incubation. The action of PDBu was half-maximal at a concentration of approximately 0.1 microM; at high concentrations, PDBu pr...
Article
The phosphorylation of proteins in the superior cervical ganglion of the rat was investigated. Ganglia were incubated with32Pi, and the32P-labeled proteins in the ganglion were separated by two-dimensional electrophoresis and visualized by autoradiography. Approximately 40 distinct phosphoproteins could be visualized by these methods. The most heav...
Article
Vasoactive intestinal peptide-like immunoreactivity (VIPLI) is not detectable in normal adult human chromaffin cells in vivo, but was demonstrated in cultured chromaffin cells from two normal adults after 22 days . Cellular content of VIPLI was markedly increased in the presence of nerve growth factor, which also stimulated neurite outgrowth. Catec...
Article
Aging rats of the Long-Evans strain spontaneously develop diffuse and nodular hyperplasia of the adrenal medulla in association with other abnormalities commonly encountered in human multiple endocrine neoplasia syndromes. The cells which comprise the adrenal nodules resemble those in the parent tumor of the rat PC12 pheochromocytoma cell line in t...
Article
Vasoactive intestinal peptide (VIP) acutely increases tyrosine hydroxylase (TH) activity in cultures of dispersed normal adult rat chromaffin cells and of PC12 rat pheochromocytoma cells. High concentrations of VIP (10 μM) produce about 3-fold increases in TH activity in both cell types. VIP also increases the content of cyclic adenosine 3′:5′-mono...
Article
Serotonin (5-HT) in the guinea pig celiac-superior mesenteric plexus was quantitatively measured by HPLC and visualized by an immunohistochemical method. Preincubation of the ganglia in a Krebs solution containing L-tryptophan and pargyline markedly elevated the content of 5-HT and K+ solution caused a release of 5-HT into the incubation medium. 5-...
Article
Previous studies have shown that muscarine increases the incorporation of 32Pi and [3H]inositol into phosphatidylinositol in the superior cervical ganglion of the rat. Because the first event in agonist-stimulated phospholipid turnover is thought to be the hydrolysis of phosphatidylinositol or of phosphatidylinositol phosphates, we measured the acc...
Article
The effect of nerve stimulation on inositol phospholipid hydrolysis in autonomic tissue was assessed by direct measurement of [3H]inositol phosphate production in ganglia that had been preincubated with [3H]inositol. Within minutes, stimulation of the preganglionic nerve increased the [3H]inositol phosphate content of the superior cervical sympathe...
Article
Incubation of the rat superior cervical ganglion in Na+-free or low-Na+ medium increased the rate of synthesis of 3,4-dihydroxyphenylalanine (DOPA) in the ganglion fourfold and caused a concomitant stable activation of tyrosine hydroxylase. DOPA synthesis was half-maximal in medium containing about 20 mM Na+. Low-Na+ medium also increased the incor...
Chapter
Muscarine stimulates the incorporation of 32P. and [3 H]inositol into phosphatidylinositol in the superior cervical ganglion of the rat. Muscarine also increases the accumulation of [3H]inositol-1-phosphate in ganglia in which the inositol-containing phospholipids were pre-labeled by incubation with [3H]inositol. The production of [3H]inositol-1-ph...
Article
Full-text available
Electrical stimulation of the superior cervical ganglion of the rat increased the phosphorylation of tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2) in this tissue. Ganglia were incubated with [32P]Pi for 90 min and were then electrically stimulated via the preganglionic nerve. Tyrosine hydroxylase was isolated from homogenates of the...
Article
Myosin was isolated from extracts of a clonal cell line of pheochromocytoma (PC12) cells by ammonium sulfate fractionation and gel filtration. This myosin consisted of heavy chains and two light chains (20 and 17 kDa). The 20 kDa light chain could be phosphorylated by a protein kinase which was also present in the extracts and which eluted after my...
Article
We studied the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion of the rat. Ganglia were preincubated with [32P]Pi and were then incubated in non-radioactive medium containing a variety of agents that are known to activate tyrosine hydroxylase in this tissue. Tyrosine hydroxylase was isolated from homogenates of the ganglia...
Article
Both dimethylphenylpiperazinium (DMPP), a nicotinic agonist, and bethanechol, a muscarinic agonist, increase 3,4-dihydroxyphenylalanine (DOPA) synthesis in the superior cervical ganglion of the rat. DMPP causes approximately a fivefold increase in DOPA accumulation in intact ganglia whereas bethanechol causes about a two-fold increase in DOPA accum...
Article
Full-text available
Neoplastic chromaffin cells from human pheochromocytomas can exhibit extensive spontaneous and nerve growth factor (NGF)-induced outgrowth of neurite-like processes in vitro, despite the absence of such processes in vivo. To determine whether acquisition of neuron-like features by human pheochromocytoma cells in culture is accompanied by functional...
Article
The urinary excretion pattern of catecholamines and their metabolites was studied in rats bearing a subcutaneous transplantable phaeochromocytoma. Compared with normal rats, tumour-bearing animals showed a markedly raised excretion of dopamine, noradrenaline and adrenaline, together with certain of their major acidic and alcoholic metabolites. No e...
Article
Muscarinic agonists cause a stable activation of tyrosine 3-monooxygenase in the superior cervical ganglion and increase the incorporation of 32Pi into phospholipids in the ganglion. We have studied the relationship between muscarine-stimulated phospholipid turnover and the muscarine-induced activation of tyrosine 3-monooxygenase. Both effects of m...
Article
We have investigated the effect of veratridine on DOPA (3,4-dihydroxyphenylalanine) accumulation by the superior cervical ganglion of the rat. Incubation of the ganglion with veratridine (50 microM) causes a 10-fold increase in the rate of DOPA accumulation. Veratridine-stimulated DOPA accumulation is blocked by tetrodotoxin, but not by cholinergic...
Article
We have studied the roles of nicotinic and muscarinic receptors in the acetylcholine-evoked secretion of catecholamine from guinea-pig chromaffin cells. Isolated guinea-pig chromaffin cells secrete catecholamine in response to acetylcholine, nicotine, and a variety of muscarinic agonists. Optimal concentrations of acetylcholine (50-200 microM) indu...
Article
We have investigated the process of catecholamine uptake in guinea-pig chromaffin cells. Isolated guinea-pig chromaffin cells accumulate [3H]norepinephrine and [3H]epinephrine by a saturable transport system. Catecholamine uptake is dependent upon temperature, energy, and extracellular Na+. The apparent KmS for norepinephrine and epinephrine transp...
Article
Adenylate cyclase activity in cell-free homogenates of the rat superior cervical ganglion (SCG) was assayed under a variety of experimental conditions. Adenylate cyclase activity was decreased by approximately one-half when 1 mM EGTA was included in the homogenization buffer and assay mixture, indicating the presence of a Ca2+-sensitive adenylate c...
Article
The rate of dopa synthesis in the rat superior cervical ganglion was increased 4- to 6-fold during continuous electrical stimulation of the cervical sympathetic trunk at 10 Hz for 30 min. This increase was only partially blocked by 3 mM hexamethonium and was not significantly affected by 6 microM atropine. In the presence of both hexamethonium and...
Article
Glucocorticoids, cholera toxin, and high plating density all increase the activity of tyrosine 3-monooxygenase (TH) in cultured PC12 pheochromocytoma cells. Glucocorticoids increase enzyme activity in cells treated with cholera toxin and in cells grown at high plating density. Glucocorticoids also increase the content of stored catecholamines in th...
Article
The activity of tyrosine 3-monooxygenase in rat superior cervical ganglia in vitro was measured by monitoring their rate of dopa production. Cholinergic agonists produce a rapid and reversible increase in dopa synthesis in the ganglia. Carbachol (0.1 mM) causes a 5- to 6-fold increase in dopa synthesis. The action of carbachol is largely inhibited...
Article
Pheochromocytoma cells contain amine oxidase (flavin-containing), and convert dopamine and norepinephrine to deaminated metabolites. Dihydroxyphenylacetic acid is the major dopamine metabolite produced by the cells, whereas dihydroxyphenylglycol is the predominant metabolite of norepinephrine. Cells incubated under control conditions produce deamin...
Article
Normal postnatal rat chromaffin cells and rat pheochromocytoma cells are known to show extensive Nerve Growth Factor (NGF)-induced process outgrowth in culture, and this outgrowth from the postnatal chromaffin cells is abolished by the corticosteroid dexamethasone. To determine whether adult rat chromaffin cells respond to NGF and dexamethasone, di...
Article
The carboxylic ionophore monensin inhibits the activity of tyrosine 3-monooxygenase and decreases the rate of catecholamine synthesis in pheochromocytoma cells incubated in vitro. The ionophore inhibits dopa production in intact pheochromocytoma cells, but does not itself inhibit tyrosine 3-monooxygenase and does not produce a stable inactivation o...

Network

Cited By