J B Furness

University of Melbourne, Melbourne, Victoria, Australia

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Publications (378)1164.16 Total impact

  • R. V. Pustovit, J. B. Furness, L. R. Rivera
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    ABSTRACT: Background Despite constipation being a common problem, the treatments that are available have side effects and are only partly effective. Recent studies show that centrally penetrant ghrelin receptor agonists cause defecation in humans and other species. Here, we describe some features of a rat model of low fiber-induced constipation, and investigate the effectiveness of the ghrelin agonist, capromorelin.Methods Rats were given low-fiber diets for 5 weeks. Their colorectal responsiveness to distension and to a behavioral test, water avoidance and colon histology were compared to those of rats on a standard diet.Key ResultsAfter the low-fiber diet, distension of the colon produced fewer propulsive contractions, behaviorally induced defecation was reduced, and the lining of the colorectum was inflamed. However, capromorelin was similarly effective in causing defecation in constipated and non-constipated rats.Conclusions & InferencesLow-fiber diet in rats produces a constipation phenotype, characterized by reduced responsiveness of the colorectum to distension and to a behavioral stimulus of defecation, water avoidance. The effectiveness of capromorelin suggests that centrally penetrant ghrelin receptor stimulants may be effective in treating constipation.
    Neurogastroenterology and Motility 01/2015; DOI:10.1111/nmo.12517 · 3.42 Impact Factor
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    ABSTRACT: Introduction: Heat stress (HS) compromises intestinal barrier integrity by inducing oxidative stress. Our objective was to evaluate whether supra‐physiological dietary supplementation of selenium (Se) and Vitamin E (VE) can protect gut barrier integrity in heat stressed pigs. Material and methods: Forty‐eight gilts (av. 22.4 kg) were randomly assigned to four diets containing 0.2 ppm Se and 17 IU VE/kg (control), 0.3 ppm Se and 50 IU VE/kg, 0.5 ppm Se and 100 IU VE/kg, or 1.0 ppm Se and 200 IU VE/kg. After 14 d supplementation, six pigs from each dietary group were allocated to climate‐controlled rooms at 20°C (thermoneutral, TN) or HS (35°C, 9 am‐5 pm/ 28°C, rest of day) for 2 d. Respiration rate (RR) and rectal temperature (RT) were monitored between 9 am and 5 pm. After 48 h, pigs were euthanized and small intestinal weights were recorded. Trans‐epithelial resistance (TER) and FITC‐dextran (4 kDa; FD4) permeability were measured in jejunum and ileum samples using an Ussing chamber. Data were analyzed by linear mixed model in Genstat. Results and discussion: Pigs under HS condition had increased RT (P=0.01), RR (P=0.01), FD4 permeability (P=0.03), and decreased TER (P=0.03). Small intestinal weight was not affected (P=0.11). With increasing dose of anti‐oxidants the effects of HS were reduced, as characterized by enhanced TER and lowered FD4 permeability (P=0.02 for both). The highest two doses of anti‐oxidants ameliorated the effects of HS on intestinal integrity. In conclusion, supraphysiological supplementation of Se and VE alleviate heat stress damage to intestinal barrier integrity.
    Digestive Physiology of Pigs, Kliczkow, Poland; 01/2015
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    ABSTRACT: Introduction: Our experiment showed antioxidants supplementation improved intestinal trans-epithelial resistance (TER) in pigs under heat stress (HS), which is hypothetically due to alleviation of HS-induced oxidative stress (OS). Material and methods: Forty-eight gilts (av. 22.4 kg) were randomly assigned to four diets containing 0.2 ppm Selenium (Se) and 17 IU Vitamin E (VE)/kg (control), 0.3 ppm Se and 50 IU VE/kg, 0.5 ppm Se and 100 IU VE/kg, or 1.0 ppm Se and 200 IU VE/kg. After 14d supplementation, six pigs from each dietary treatment were allocated to climate-controlled rooms at 20°C (thermoneutral) or HS (35°C, 9am-5pm/ 28°C, rest of day) for 2d. Glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD), oxidized glutathione (GSSG), and total glutathione (GSH) were measured in jejunum and ileum homogenates. Data were analysed by ANOVA and correlation in Genstat 16th edition. Results and Discussion: HS attenuated GPx (P<0.01), but not GST or SOD activities. HS induced OS as HS tended to increase GSSG concentration (P=0.08) and increased GSSG/total GSH ratio (P<0.05). Along with increasing dosages, antioxidants linearly improved GPx activity (P<0.05), decreased GSSG (P=0.06) and GSSG/total GSH ratio (P<0.05), but not affect SOD and GST. The highest dose of antioxidants had higher GPx activity (P<0.05), lower GSSH (P=0.06) and GSSG/total GSH ratio (P<0.05) than control diet under HS. GPx and GST activities moderately correlated with TER (correlation=0.45 and -0.44, respectively). In conclusion, 1.0 ppm Se and 200 IU/kg VE alleviated HS-induced OS by improving GPx activity, which partially explained the maintained TER during HS.
    Digestive Physiology of Pigs, Kliczkow, Poland; 01/2015
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    J. B. Furness, J.J. Cottrell, D. M. Bravo
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    ABSTRACT: Abstract Text: Intestinal L cells have key roles in the detection of the chemical environment in the gut lumen, to which they react by the release of hormones that influence appetite, proximal gut motility, insulin secretion and mucosal function (Furness et al, Nature Gastroenterology, 10, 729–740, 2013). Important amongst L cell hormones are glucagon-like peptide1 (GLP-1) and peptide tyrosine-tyrosine (PYY), which are products of separate genes. The conventional description of their localisation is that GLP-1 and PYY are in the same storage vesicles in the same cells. However, GLP-1 and PYY have different functions, particularly in relation to insulin secretion and mucosal function. We have used super-resolution (3D-SIM) microscopy and double-labelling immunohistochemistry to investigate the subcellular localisations of the hormones, and digital scanning microscopy to investigate cell populations. Super-resolution microscopy revealed that GLP-1 and PYY are in separate storage organelles in enteroendocrine cells from mouse, rat, pig and human. The majority of the organelles were 150-170 nm or less in diameter, and are concluded to be secretory vesicles. Only 10-20% of organelles had immunoreactivity for both hormones. Even this may be an overestimate, as touching or very close vesicles may not be effectively resolved, even with super-resolution microscopy. In investigating co-localisation at the cell level, we included glucagon-like insulinotropic peptide (GIP), an incretin of K cells, in the analysis. The work shows that there is a K/L cell gradient in the mouse intestine. From the duodenum to the distal colon, there are populations of cells with GIP alone, GLP alone, PYY alone and all combinations of the three hormones. Greatest numbers of GIP cells were in the doudenum and jejunum, where 30-40% contained only GIP and the remainder also contained GLP-1. A small proportion also contained PYY. Similar patterns of overlap occurred in the proximal and distal ileum, where GLP-1 was the dominant peptide, which was often alone, or co-localised with PYY. In the large intestine the majority of cells contained both GLP-1 and PYY, but cells with only one of these and cells with all three hormones were found. The findings reveal a structural basis for the separate or preferential control of GLP-1, PYY (and possibly GIP) release. A number of physiological studies imply that there can be differential release of GLP-1 and PYY. This should be investigated further. Keywords: enteroendocrine cells, incretins, glucagon like peptide, peptideYY
    2014 ADSA-ASAS-CSAS Joint Annual Meeting; 07/2014
  • John Furness
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    ABSTRACT: Abstract Text: The optimal utilisation of nutrients requires an integrated response of the gastrointestinal tract to ingested food. Broad mechanisms are similar in all mammals, and involve sensing food components through olfaction, taste and specialised receptors within the stomach and intestines. The sensing of food components leads to release of gut hormones and activation of nerves, which in turn modify digestive functions. Bacteria, viruses, fungi and potentially injurious substances in foods activate tissue defence mechanisms. While the responses to nutrients lead to broadly similar changes in appetite, satiety and food-seeking behaviour, gastrointestinal motility, release of digestive enzymes and induction of nutrient transporters, the requirements in different animals differ. To simplify discussion, we can divide species into ruminant foregut fermenters (such as cattle and sheep), non-ruminant foregut fermenters (e.g., kangaroo, colobus monkey), hind-gut fermenters (such as horse), and auto-enzyme dependent digesters (pig, human) that also gain nutrition from hind-gut fermentation. Ruminants are efficient digesters because the rumenal movements are able to stratify food into gas, fluid and particle components, retaining food to be digested in the forestomach and passing more fully digested material into the abomasum and duodenum, and also being able to return food from the forestomach to the mouth for mastication and limited enzyme exposure. Poultry have multiple stomachs that allow for storage, digestion and tituration, but not fermentation. Ruminants lose efficiency in that most carbohydrate is utilised by gastric bacteria and very little glucose reaches the small intestine. Thus glucose must be synthesised from short chain fatty acids produced by bacteria, whereas species such as pig and human convert carbohydrate to glucose enzymatically. Thus ruminants are more prone than other groups to enter into negative glucose balance, for example during post-partum lactation. Obligatory by-products of fermentation are carbon dioxide and methane. Foregut fermenters are also advantaged by being able to readily utilise vitamins produced by fermentation. It is thought that coprophagy by hind-gut fermenters, such as rabbits, provides access to such vitamins. Foregut fermentation also contributes to detoxification, for which hindgut fermenters and autoenzymic digesters rely primarily on the liver. With these differences in mind, it is necessary to closely consider what information can be readily extrapolated between species. Conversely, we can point to similarities in neural and hormonal signalling systems and products of digestion, achieved in different ways, that are available for energy utilisation and incorporation into tissues. Keywords: digestive physiology; fermentation; glucose; comparative
    2014 ADSA-ASAS-CSAS Joint Annual Meeting; 07/2014
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    ABSTRACT: Disorders of gastrointestinal functions that are controlled by enteric neurons commonly accompany fatty liver disease. Established fatty liver disease is associated with diabetes, which itself induces enteric neuron damage. Here, we investigate the relationship between fatty liver disease and enteric neuropathy, in animals fed a high-fat, high-cholesterol diet in the absence of diabetes.
    Neurogastroenterology and Motility 06/2014; DOI:10.1111/nmo.12385 · 3.42 Impact Factor
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    ABSTRACT: Objective To analyse the temporal bones and implant of the first University of Melbourne's (UOM) patient (MC-1) to receive the multi-channel cochlear prosthesis. Methods The left cochlea was implanted with the prototype multi-channel cochlear prosthesis on 1 August 1978, and the Cochlear versions CI-22 and CI-24 on 22 June 1983 and 10 November 1998, respectively. MC-1 died in 2007. Results Plain X-rays of the temporal bones showed that after the CI-22 had been explanted seven electrode bands remained in situ. Micro-CT scans also revealed a partially united fracture transecting the left implanted and right control cochleae. Histology indicated a total loss of the organ of Corti on both sides, and a tear of the left basilar membrane. In addition, there was a dense fibrous capsule with heterotopic bone surrounding one proximal band of the CI-22 array that restricted its removal. This pathology was associated with dark particulate material within macrophages, probably due to the release of platinum from the electrode bands. Scanning electron microscopy (SEM) showed possible corrosion of platinum and surface roughening. Three-dimensional reconstruction of the cochlear histology demonstrated the position of the electrode tracts (C1-22 and CI-24) in relation to the spiral ganglion, which showed 85-90% loss of ganglion cells. Discussion and conclusions This study confirms our first histopathological findings that our first free-fitting banded electrode array produced moderate trauma to the cochlea when inserted around the scala tympani of the basal turn. The difficulty in extraction was most likely due to one band being surrounded by an unusually large amount of fibrous tissue and bone, with an electrode band caught due to surface irregularities. Some surface corrosion and a small degree of platinum deposition in the tissue may also help explain the outcome for this long-term cochlear implantation.
    Cochlear Implants International 06/2014; 15(S2). DOI:10.1179/1754762814Y.0000000087
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    ABSTRACT: Discovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side-effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action. Anesthetized rats were used to investigate sites and mechanisms of action of ulimorelin. Intravenous ulimorelin (1-5 mg/kg) caused a substantial and prolonged (~1 h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5 μg) to the lumbosacral spinal cord. Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long-lasting, in contrast with other colokinetics that target ghrelin receptors.
    Neurogastroenterology and Motility 11/2013; 26(2). DOI:10.1111/nmo.12259 · 3.42 Impact Factor
  • J B Furness, D P Poole
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    ABSTRACT: The functioning of the gastrointestinal tract is under the control of the most extensive system of peripheral neurons in the body, the enteric nervous system, and the largest endocrine system of the body, the GEP endocrine system. The enteric nervous system in large mammals contains 500 million neurons, and the GEP endocrine system produces more than 30 hormones. Numerous enteric neuropathies affecting both humans and animals have been described and digestive disorders affect commercially important species, such as horses and cattle. The most severe enteric neuropathies (e.g., lethal white syndrome in horses or Hirschsprung's disease in humans) can be fatal. Also, horses with ileus or other digestive disorders are commonly euthanized. In this review we discuss examples of enteric neuropathies that affect agricultural animals and humans: prion disease, postoperative ileus, distal enteric aganglionosis, and infective diarrhea. Enteric neurons and glia are a location of prion proteins and are involved in transmission of the infection from gut to brain and brain to gut. Postoperative ileus is a complex disorder involving the local inhibitory effects of sympathetic nervous system activation and the release of opioids, presumably from enteric neurons. Intestinal inflammation, especially of the external muscle that includes enteric ganglia, also occurs in ileus. Congenital distal bowel aganglionosis, responsible for lethal white syndrome in horses, Hirschsprung's disease in humans, and similar conditions in mice and rats, is a fatal condition if untreated. Mutations of the same genes can cause the condition in each of these species. The only effective current treatment is surgical removal of the aganglionic bowel. Infectious diarrheas involve activation of enteric secretomotor neurons by pathogens and the toxins they produce, which causes substantial fluid loss. Strategies to target enteric neurons in the treatment of secretory diarrheas have not been developed. Disorders of enteroendocrine cells, other than GEP endocrine tumors, are less well documented. However, evidence for the involvement of gut endocrine cells in a subset of patients with irritable bowel syndrome, and in the symptomology of celiac disease, has been demonstrated. Further investigation of the involvement of enteric neural and endocrine signaling systems in digestive disorders, especially in agricultural and companion animals, may lead to diagnostic and therapeutic advances.
    Journal of Animal Science 12/2011; 90(4):1203-12. DOI:10.2527/jas.2011-4825 · 1.92 Impact Factor
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    L R Rivera, D P Poole, M Thacker, J B Furness
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    ABSTRACT: Nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS) is a transmitter of inhibitory neurons supplying the muscle of the gastrointestinal tract. Transmission from these neurons is necessary for sphincter relaxation that allows the passage of gut contents, and also for relaxation of muscle during propulsive activity in the colon. There are deficiencies of transmission from NOS neurons to the lower esophageal sphincter in esophageal achalasia, to the pyloric sphincter in hypertrophic pyloric stenosis and to the internal anal sphincter in colonic achalasia. Deficits in NOS neurons are observed in two disorders in which colonic propulsion fails, Hirschsprung's disease and Chagas' disease. In addition, damage to NOS neurons occurs when there is stress to cells, in diabetes, resulting in gastroparesis, and following ischemia and reperfusion. A number of factors may contribute to the propensity of NOS neurons to be involved in enteric neuropathies. One of these is the failure of the neurons to maintain Ca(2+) homeostasis. In neurons in general, stress can increase cytoplasmic Ca(2+), causing a Ca(2+) toxicity. NOS neurons face the additional problem that NOS is activated by Ca(2+). This is hypothesized to produce an excess of NO, whose free radical properties can cause cell damage, which is exacerbated by peroxynitrite formed when NO reacts with oxygen free radicals.
    Neurogastroenterology and Motility 09/2011; 23(11):980-8. DOI:10.1111/j.1365-2982.2011.01780.x · 3.42 Impact Factor
  • Autonomic Neuroscience 09/2011; 163(s 1–2):58–59. DOI:10.1016/j.autneu.2011.05.062 · 1.37 Impact Factor
  • Autonomic Neuroscience 09/2011; 163(1):58-58. DOI:10.1016/j.autneu.2011.05.061 · 1.37 Impact Factor
  • Autonomic Neuroscience 09/2011; 163(1):69-69. DOI:10.1016/j.autneu.2011.05.090 · 1.37 Impact Factor
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    ABSTRACT: Ghrelin and ghrelin receptor agonist have effects on central neurons in many locations, including the hypothalamus, caudal brain stem, and spinal cord. However, descriptions of the distributions of ghrelin-like immunoreactivity in the CNS in published work are inconsistent. We have used three well-characterized anti-ghrelin antibodies, an antibody to the unacylated form of ghrelin, and a ghrelin peptide assay in rats, mice, ghrelin knockout mice, and ghrelin receptor reporter mice to re-evaluate ghrelin presence in the rodent CNS. The stomach served as a positive control. All antibodies were effective in revealing gastric endocrine cells. However, no specific staining could be found in the brain or spinal cord. Concentrations of antibody 10 to 30 times those effective in the stomach bound to nerve cells in rat and mouse brain, but this binding was not reduced by absorbing concentrations of ghrelin peptide, or by use of ghrelin gene knockout mice. Concentrations of ghrelin-like peptide, detected by enzyme-linked immunosorbent assay in extracts of hypothalamus, were 1% of gastric concentrations. Ghrelin receptor-expressing neurons had no adjacent ghrelin immunoreactive terminals. It is concluded that there are insignificant amounts of authentic ghrelin in neurons in the mouse or rat CNS and that ghrelin receptor-expressing neurons do not receive synaptic inputs from ghrelin-immunoreactive nerve terminals in these species.
    Neuroscience 07/2011; 193:1-9. DOI:10.1016/j.neuroscience.2011.07.063 · 3.33 Impact Factor
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    ABSTRACT: Animal proof of principle study. To determine whether capromorelin, a compound that causes defecation by stimulating ghrelin receptors within the lumbosacral defecation centers, is effective after spinal cord injury (SCI), and whether SCI significantly alters sensitivity to the compound. University of Melbourne and Austin Hospital, Melbourne, Australia. Rats were subjected to spinal cord contusion injury or were sham-operated. At 6 weeks after surgery, effects of capromorelin on blood pressure, heart rate and propulsive contractions of the colorectum were investigated. Capromorelin caused robust propulsive activity in the colorectum soon after its application. The compound was similarly effective in naïve, sham-operated and spinal cord-injured rats. Blood pressure increases caused by capromorelin were not exaggerated after SCI, and there was no evidence of phasic blood pressure increases when the colon was contracted by the compound. Capromorelin is a therapeutic compound that could potentially be used to relieve constipation by triggering defecation in spinal cord-injured patients.
    Spinal Cord 05/2011; 49(10):1036-41. DOI:10.1038/sc.2011.60 · 1.70 Impact Factor
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    M Thacker, L R Rivera, H-J Cho, J B Furness
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    ABSTRACT: Damage to mucosal epithelial cells, muscle cells and enteric neurons has been extensively studied following intestinal ischemia and reperfusion (I/R). Interestingly, the effects of intestinal I/R on enteric glia remains unexplored, despite knowledge that glia contribute to neuronal maintenance. Here, we describe structural damage to enteric glia and associated changes in distribution and immunoreactivity of the neuronal protein Hu. The mouse small intestine was made ischemic for 3 h and reperfused from 1 to 12 h. Immunohistochemical localisation of glial fibrillary acidic protein (GFAP), Hu and TUNEL were used to evaluate changes. At all time points glial cells became distorted, which was evident by their altered GFAP immunoreactivity, including an unusual appearance of bright perinuclear GFAP staining and the presence of GFAP globules. The numbers of neurons per ganglion area were significantly fewer in ganglia that contained distorted glia when compared with ganglia that contained glia of normal appearance. The distribution of Hu immunoreactivity was altered at all reperfusion time points. The presence of vacuoles and Hu granules in neurons was evident and an increase in nuclear Hu, relative to cytoplasmic Hu, was observed in ganglia that contained both normal and distorted glial cells. A number of neurons appeared to lose their Hu immunoreactivity, most noticeably in ganglia that contained distorted glial cells. TUNEL reaction occurred in a minority of glial cells and neurons. Structural damage to gliofilaments occurs following I/R and may be associated with damage to neighboring neurons.
    Neurogastroenterology and Motility 03/2011; 23(11):e500-9. DOI:10.1111/j.1365-2982.2011.01696.x · 3.42 Impact Factor
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    ABSTRACT: We have previously demonstrated that a centrally penetrant ghrelin receptor agonist enhances colorectal motility, through activation of the lumbo-sacral defecation center (L6-S1 region of the spinal cord) in rats. In the present study, we examined the effects of the native peptide and its non-acylated counterpart in eliciting this stimulatory effect on colorectal motility. Rats were anesthetised with α-chloralose and ketamine, and colorectal intraluminal pressure and propelled intraluminal liquid volume were recorded in vivo. Intrathecal application of acylated ghrelin to the L6-S1 region of the spinal cord, but not intravenous application, elicited groups of phasic increases in colorectal intraluminal pressure that were associated with increased fluid output through the anal cannula. The effect was dose-dependent. The colokinetic effects of ghrelin were prevented if the pelvic nerves were severed. Reverse transcription polymerase chain reaction revealed the expression of the ghrelin and ghrelin receptor genes in the lumbo-sacral spinal cord. In contrast to acylated ghrelin, des-acyl ghrelin failed to cause changes in colorectal motility. However, when des-acyl ghrelin and ghrelin were applied simultaneously at the L6-S1 region, the ghrelin-induced enhancement of colorectal motility was significantly attenuated. It is concluded that acylation of the ghrelin peptide is essential to promote propulsive contractions of the colorectum and that des-acyl ghrelin opposes this effect. At most other sites of ghrelin action, des-acyl ghrelin either has no effect or it mimics ghrelin. This is the first evidence that non-acylated ghrelin opposes the action of the acylated peptide in the spinal cord.
    Neurogastroenterology and Motility 10/2010; 22(10):1124-31. DOI:10.1111/j.1365-2982.2010.01553.x · 3.42 Impact Factor
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    ABSTRACT: The intrinsic primary afferent neurons (IPANs) in the intestine are the first neurons of intrinsic reflexes. Action potential currents of IPANs flow partly through calcium channels, which could feasibly be targeted by pregabalin. The aim was to determine whether pregabalin-sensitive α2δ1 subunits associate with calcium channels of IPANs and whether α2δ1 subunit ligands influence IPAN neuronal properties. We used intracellular electrophysiological recording and in situ hybridisation to investigate calcium channel subunit expression in guinea-pig enteric neurons. Key The α subunits of N (α1B) and R (α1E) type calcium channels, and the auxiliary α2δ1 subunit, were expressed by IPANs. This is the first discovery of the α2δ1 subunit in enteric neurons; we therefore investigated its functional role, by determining effects of the α2δ1 subunit ligand, pregabalin, that inhibits currents carried by channels incorporating this subunit. Pregabalin (10 μmol L(-1)) reduced the action potential duration. The effect was not increased with increase in concentration to 100 μmol L(-1). If N channels were first blocked by ω-conotoxin GVIA (0.5 μmol L(-1)), pregabalin had no effect on the residual inward calcium current. Reduction of the calcium current by pregabalin substantially inhibited the after-hyperpolarising potential (AHP) and increased neuron excitability. Intrinsic primary afferent neurons express functional N (α1B) channel-forming subunits that are associated with α2δ1 modulatory subunits and are inhibited by pregabalin, plus functional R (α1E) channels that are not sensitive to binding of pregabalin to α2δ subunits. The positive effects of pregabalin in irritable bowel syndrome (IBS) patients might be partly mediated by its effect on enteric neurons.
    Neurogastroenterology and Motility 10/2010; 22(10):e301-8. DOI:10.1111/j.1365-2982.2010.01567.x · 3.42 Impact Factor
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    ABSTRACT: The distribution and chemical phenotypes of sympathetic and dorsal root ganglion (DRG) neurons innervating the equine ileocecal junction (ICJ) were studied by combining retrograde tracing and immunohistochemistry. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) was investigated. Sympathetic neurons projecting to the ICJ were distributed within the celiac (CG), cranial mesenteric (CranMG), and caudal mesenteric (CaudMG) ganglia, as well as in the last ganglia of the thoracic sympathetic chain and in the splanchnic ganglia. In the CG and CranMG 91 +/- 8% and 93 +/- 12% of the neurons innervating the ICJ expressed TH- and DBH-IR, respectively. In the CaudMG 90 +/- 15% and 94 +/- 5% of ICJ innervating neurons were TH- and DBH-IR, respectively. Sympathetic (TH-IR) fibers innervated the myenteric and submucosal ganglia, ileal blood vessels, and the muscle layers. They were more concentrated at the ICJ level and were also seen encircling myenteric plexus (MP) and submucosal plexus (SMP) descending neurons that were retrogradely labeled from the ICJ. Among the few retrogradely labeled DRG neurons, nNOS-, CGRP-, and SP-IR nerve cells were observed. Dense networks of CGRP-, nNOS-, and SP-IR varicosities were seen around retrogradely labeled prevertebral ganglia neurons. The CGRP-IR fibers are probably the endings of neurons projecting from the intestine to the prevertebral ganglia. These findings indicate that this crucial region of the intestinal tract is strongly influenced by the sympathetic system and that sensory information of visceral origin influences the sympathetic control of the ICJ.
    The Journal of Comparative Neurology 10/2010; 518(19):4046-66. DOI:10.1002/cne.22443 · 3.51 Impact Factor

Publication Stats

18k Citations
1,164.16 Total Impact Points


  • 1969–2015
    • University of Melbourne
      • • Department of Anatomy and Neuroscience
      • • School of Botany
      • • Department of Physiology
      • • Department of Zoology
      Melbourne, Victoria, Australia
  • 1970–2011
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
  • 1993
    • Flinders Medical Centre
      Tarndarnya, South Australia, Australia
  • 1991
    • The Royal Children's Hospital
      Melbourne, Victoria, Australia
  • 1978–1991
    • Flinders University
      • • School of Medicine
      • • Department of Anatomy and Histology
      • • Centre for Neuroscience
      Tarndarnya, South Australia, Australia
  • 1986
    • Neuroscience Research Australia
      Sydney, New South Wales, Australia
  • 1982
    • University of South Australia
      Tarndarnya, South Australia, Australia
  • 1980
    • National Institute of Mental Health (NIMH)
      • Laboratory of Clinical Science
      Maryland, United States
    • University of Oxford
      • Department of Pharmacology
      Oxford, England, United Kingdom
  • 1977
    • Prince Henry's Institute
      Melbourne, Victoria, Australia
  • 1972
    • University of Birmingham
      Birmingham, England, United Kingdom