Ulrich Gergs's research while affiliated with Martin Luther University Halle-Wittenberg and other places

Publications (111)

Preprint
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Cantharidin, an inhibitor of protein phosphatases 1 and 2A (PP1, PP2A), is known to increase force of contraction and to shorten time of relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human atrial preparations (HAP). During bypass-surgery trabeculae carneae from human right a...
Article
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Levosimendan (up to 10 µM) given alone failed to increase force of contraction in isolated electrically stimulated (1 Hz) left atrial (LA) preparations from wild-type mice. Only in the additional presence of 0.1 µM rolipram, an inhibitor of the activity of phosphodiesterase IV, levosimendan increased force of contraction in LA and increased the pho...
Article
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Heart failure is a syndrome that can result from impaired heart muscle contractions like in dilative cardiomyopathy but also from hypertrophic obstructive cardiomyopathy (HOCOM). A pharmacological therapy might lie in Ca ²⁺ -sensitizing or Ca ²⁺ -desensitizing drugs, respectively. Such drugs are thought to be omecamtiv mecarbil (OME) and mavacamten...
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The use of recreational drugs like ephedrine, norephedrine, 3,4-methylenedioxymethamphetamine (MDMA), and mescaline can lead to intoxication and, at worst, to death. One reason for a fatal course of intoxication with these drugs might lie in cardiac arrhythmias. To the best of our knowledge, their inotropic effects have not yet been studied in isol...
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Calsequestrin (CSQ2) is the main Ca²⁺-binding protein in the sarcoplasmic reticulum of the mammalian heart. In order to understand the function of calsequestrin better, we compared two age groups (young: 4–5 months of age versus adult: 18 months of age) of CSQ2 knock-out mice (CSQ2(−/−)) and littermate wild-type mice (CSQ2(+/+)). Using echocardiogr...
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Reversible protein phosphorylation is a posttranslational modification of regulatory proteins involved in cardiac signaling pathways. Here, we focus on the role of protein phosphatase 2A (PP2A) for cardiac gene expression and stress response using a transgenic mouse model with cardiac myocyte-specific overexpression of the catalytic subunit of PP2A...
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A2A adenosine receptors (A2A-AR) have a cardio-protective function upon ischemia and reperfusion, but on the other hand, their stimulation could lead to arrhythmias. Our aim was to investigate the potential use of the PET radiotracer [18F]FLUDA to non-invasively determine the A2A-AR availability for diagnosis of the A2AR status. Therefore, we compa...
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This review addresses pharmacological, structural and functional relationships among H 2 -histamine receptors and H 1 -histamine receptors in the mammalian heart. The role of both receptors in the regulation of force and rhythm, including their electrophysiological effects on the mammalian heart, will then be discussed in context. The potential cli...
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In the past, we generated transgenic mice that overexpress the human histamine 2 (H 2 )-receptor (H 2 -TG) or that overexpress the human serotonin 4 (5-HT 4 )-receptor (5-HT 4 -TG) in the heart. Here, we crossbred these lines of mice to generate double transgenic mice that overexpress both receptors (DT). This was done to study a conceivable intera...
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Heat shock protein (HSP) 70 is a molecular chaperone that regulates protein structure in response to thermal stress. In addition, HSP70 is involved in post-translational modification and is related to the severity of some diseases. Here, we tested the functional relevance of long-lasting HSP70 expression in a model of nonischemic heart failure usin...
Article
In an integrative approach, we studied cardiac effects of recently published novel H2 receptor agonists in the heart of mice that overexpress the human H2 receptor (H2-TG), littermate wild type control mice (WT) and in isolated electrically driven muscle preparations from patients undergoing cardiac surgery. Under our experimental conditions, the H...
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Histamine is known to lead to arrhythmias in the human heart. A mouse model to mimic these effects has hitherto not been available but might be useful to study the mechanism(s) of H 2 -histamine receptor-induced arrhythmias and may support the search for new antiarrhythmic drugs. In order to establish such a model in mice, we studied here the incid...
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As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated transgenic mice with cardiac muscle cell-specific overexpression of PP2Acα (PP2A) and PP5 (PP5). For further studies we crossbred PP2A and PP5 mice to obtain PP2AxPP5 double transgenic mice (PP2AxPP...
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Histamine exerts cAMP-dependent positive inotropic effects (PIE) and positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic mice which overexpress the human H 2 -receptor in the heart (=H 2 -TG). To determine whether these effects are antagonized by phosphodiesterases (PDEs), contractile studies were done...
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We have previously shown that histamine (2-(1 H -imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (H 2 R-TG) mice that overexpress the human H 2 histamine receptor (H 2 R) in the heart; however, the effects...
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The current study aimed to deepen our knowledge on the role of cardiac 5-HT4 receptors under pathophysiological conditions. To this end, we used transgenic (TG) mice that overexpressed human 5-HT4a receptors solely in cardiac myocytes (5-HT4-TG mice) and their wild-type (WT) littermates that do not have functional cardiac 5-HT4 receptors as control...
Article
Protein phosphatases are important, for example, as functional antagonists of β-adrenergic stimulation of the mammalian heart. While β-adrenergic stimulations increase the phosphorylation state of regulatory proteins and therefore force of contraction in the heart, these phosphorylations are reversed and thus force is reduced by the activity of pro...
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Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this metabolism in the mammalian heart in vivo is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2-histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in...
Article
We investigated whether hypothermia would be arrhythmogenic in mice that overexpress the human 5-HT4 receptor only in their cardiac myocytes (5-HT4-TG). Contractile studies were performed in isolated, electrically driven (1 Hz) left and spontaneously beating right atrial preparations of 5-HT4-TG and littermate wild-type control mice (WT). Hypotherm...
Article
It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT4-receptors. Therefore, we studied transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes in the atrium and in the ventricle (5-HT4-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopram...
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This review presents an overview of cardiac A 2A -adenosine receptors The localization of A 2A -AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted. The putative signal transduction systems of A 2A -AR in cells in the living heart, as well as the known interactio...
Preprint
BACKGROUND There remain doubts about whether multiple choice answer formats (single choice) offer the best option to encourage deep learning or whether SC formats simply lead to superficial learning or cramming. Moreover, cueing is always a drawback in the SC format. Another way to assess knowledge is true multiple-choice questions in which one or...
Article
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Single best answers (single choice, SC) are the classical tools used in medical examinations on all levels of education. In contrast, very short answer (VSA) probably requires sound prior knowledge and deeper learning than SC, and VSA should make cueing and guessing impossible. Hence, in a basic pharmacology course, we wanted to compare the SC and...
Article
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As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated mice with cardiac-specific overexpression of PP2Cβ (PP2C-TG) and compared them with littermate wild type mice (WT) serving as a control. Cardiac fibrosis was noted histologically in PP2C-TG. Collage...
Article
We studied transgenic mice with cardiac-specific overexpression of H2-histamine receptors (H2-TG) by using the alpha myosin heavy chain promoter. We wanted to address whether this overexpression would protect the heart against paradigmatic stressors. To this end, we studied isolated atrial preparations in an organ bath under normoxic and hypoxic co...
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Chloroform has been used over decades in anesthesia before it was replaced by other volatile anesthetics like halothane or sevoflurane. Some of the reasons were inadmissible side effects of chloroform like bradycardia or neural illness. In the present study, we identified members of the G protein-activated inwardly rectifying potassium channel fami...
Poster
In Sf9 insect cells, other have noted that amitriptyline inhibits potently expressed human histamine H2 receptors. Here, we examined the effect of amitriptyline in left atrial force and right atrial beating rate in a transgenic mouse model (TG) with cardiac overexpression of the human histamine H2 receptor.
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We wanted to test the progress of medical students at our university in a pharmacology course. The formal teaching was given as lectures to the full class of students. We gave the very same written test of multiple-choice (MC) questions (single best choice) to third-year medical students before and after a one semester course of basic pharmacology....
Article
Objectives: To reduce the incidence of peri- or postoperative infections in orthopaedic surgery, patients are prophylactically treated with antibiotics. Here, we wanted to know whether effective bone and intervertebral disc concentrations of cefuroxime are reached. Methods: Patients undergoing surgery of hip (N = 40; 62.5% male) or spine (N = 40...
Article
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Adenosine can be released from the heart and may stimulate four different cardiac adenosine receptors. A receptor subtype that couples to the generation of cyclic adenosine monophosphate (cAMP) is the A2A-adenosine receptor (A2A-AR). To better understand its role in cardiac function, we studied mechanical and electrophysiological effects in transge...
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The pathophysiological mechanisms of sepsis-induced cardiac dysfunction are largely unknown. The Toll-like receptor 4 (TLR4) is expressed in cardiac myocytes and is involved in bacterial endotoxin-mediated inflammatory disorders. TLR4 signaling leads to activation of the nuclear factor kappa B followed by increased expression of cytokines. Several...
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Serotonin (5-hydroxy-tryptamine, 5-HT) exerted concentration-dependent positive inotropic effects or positive chronotropic effects in transgenic (TG) mice which overexpress the human 5-HT4a receptor in the heart but not in littermate wild-type (WT) mice. These positive inotropic effects and positive chronotropic effects are thought to be mediated b...
Article
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Uridine 5'-triphosphate (UTP) exerts a positive inotropic effect (PIE) in isolated electrically driven isolated right atrial trabeculae carneae from patients undergoing heart surgery. This review discusses some aspects of the current knowledge on the putative receptor(s) involved and the potential biochemical transduction steps leading to the PIE.
Article
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The mature mammalian myocardium contains composite junctions (areae compositae) that comprise proteins of adherens junctions as well as desmosomes. Mutations or deficiency of many of these proteins are linked to heart failure and/or arrhythmogenic cardiomyopathy in patients. We firstly wanted to address the question whether the expression of these...
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After the publication of this article, the authors noticed an error in one of the grant numbers (2015R1A2A1A05001708) in the Acknowledgements section.
Article
In an integrative approach, we studied the role of histamine H2 receptors in the mouse heart. We noted that histamine, added cumulatively to the organ bath, failed to affect the force of contraction in left atrial preparations and did not change spontaneous heart rate in right atrial preparations from wild-type mice. By contrast, in the same prepar...
Article
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Heart failure and aging of the heart show many similarities regarding hemodynamic and biochemical parameters. There is evidence that heart failure in experimental animals and humans is accompanied and possibly exacerbated by increased activity of protein phosphatase (PP) 1 and/or 2A. Here, we wanted to study the age-dependent protein expression of...
Article
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Cisapride and prucalopride act as 5-HT4 receptor agonists. As a part of our ongoing effort to study the utility of a transgenic (TG) mouse model overexpressing cardiac 5-HT4 receptors, we assessed the extent to which we could recapitulate cisapride and prucalopride agonists. Contractile studies were performed using isolated left and right atrial pr...
Article
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About half of the cardiac serine/threonine phosphatase activity is due to the activity of protein phosphatase type 1 (PP1). The activity of PP1 can be inhibited by an endogenous protein for which the expression inhibitor-2 (I-2) has been coined. We have previously described a transgenic mouse overexpressing a truncated form of I-2. Here, we have de...
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Multiple-choice questions are widely used in clinical education. Usually, the students have to mark the one and only correct answer from a set of five alternatives. Here, in a voluntary exam, at the end of an obligatory pharmacology exam, we tested a format where more than one alternative could be correct ( N=544 students from three year groups). M...
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A regulatory mechanism that controls how cardiac muscle responds to stress could inform development of new therapies for preventing heart failure. Physiological stimuli ranging from heavy exercise to heart attack can induce hypertrophy, an increase in cardiac muscle mass that is initially beneficial but can lead to organ failure. Researchers led by...
Article
We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather...
Article
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Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and dephosphorylates the elastic N2B-uni...
Article
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Background: Adenosine can be produced in the heart and acts on cardiac adenosine receptors. One of these receptors is the A2A-adenosine receptor (A2A-AR). Methods and Results: To better understand its role in cardiac function, we generated and characterized mice (A2A-TG) which overexpress the human A2A-AR in cardiomyocytes. In isolated atrial prepa...
Article
Patients undergoing hip or knee replacement therapy are routinely pretreated with antibiotics before they enter the operation theater. This treatment intends to reduce the incidence of peri- or postsurgical infections. Here, we calculated the uptake kinetics of levofloxacin into bone to see whether levofloxacin could be obtained from the trabecular...
Article
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In the human cardiovascular system, serotonin (5-HT) exerts positive inotropic and chronotropic effects mediated by 5-HT4 receptors. Moreover, 5-HT4 receptor stimulation can cause arrhythmias in the human heart. Response to 5-HT can fade due to desensitization of the receptor system and/or activation of phosphodiesterases. In this study, we investi...
Article
Using transgenic mice (TG) that overexpress the human 5-HT4a-receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor, 5-hydroxy-tryptophan (5-HTP), can exert in...
Article
Aim: Several genetically modified mice models were studied so far to investigate the role of cardiac calsequestrin (CSQ2) for the contractile function of the ventricle and for the occurrence of ventricular tachycardia. By using a CSQ2 knockout mouse we wanted to study also the atrial function of CSQ2. Methods: The influence of CSQ2 on atrial fun...
Article
Background/objectives: Increased activity of cardiac protein phosphatases is an important feature in human heart failure. Several different protein phosphatases (PP) are involved in the regulation of excitation-contraction-coupling of the myocardium. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase consisting of a dimeric core enzym...
Article
Development of a transgenic animal model always is followed by extensive characterization steps. Here, we intended to test and optimize a fast screening method to get general findings about the differential protein composition in the heart of wild type (WT) and transgenic (TG) mice. Therefore, we developed a protocol for magnetic bead-based separat...
Article
Objectives Patients undergoing hip or knee replacement therapy are routinely pretreated with antibiotics before surgery. It is controversial in which antibiotic is the treatment of choice for this purpose. One possibility is the cephalosporin ceftriaxone. Here, we wanted to know if effective tissue concentrations are reached. Methods We studied pla...
Article
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death especially in times of increased sympathetic tone, for example, during sports, which have been confirmed by nuclear imaging studies. However, the underlying biochemical pathways remain to be delineated. Therefore, we investigated the expression leve...