Receptor mechanisms involved in the 5‐HT‐induced inotropic action in the rat isolated atrium

Läer, Stephanie; Remmers, Freerk Ole; Scholz, Hasso; Stein, Birgitt; Müller, Frank; Neumann, Joachim

doi:10.1038/sj.bjp.0701702

Cited by 47 publications

(39 citation statements)

References 37 publications

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“…Taken together, these data might explain, at least in part, why many transmitters and hormones coupling to the PIP 2 -PLC-IP 3 cascade exert comparatively large positive inotropic effects in the atrium but only small or no positive inotropic effects in the ventricle (e.g. angiotensin II [131] or 5-hydroxytryptamine [124]). IP 3 does not alter myofilament Ca 2+ responsiveness [48].…”

Section: Ip 3 Signaling In Atrial Myocytesmentioning

confidence: 91%

“…The atrial myocardium expresses numerous receptors coupling to the PIP 2 -PLC-IP 3 cascade. Increased phosphoinositide breakdown and inositol phosphate generation in atrium is mediated by receptors for acetylcholine (muscarinic, M 1 and M 3 ), angiotensin II (AT 1 ), endothelin (ET A ), histamine (H 1 ), 5-hydroxytryptamine (5-HT 2 ), norepinephrine (α 1 ) and vasopressin in various species including cat, chick, guinea-pig, mouse, rat and human [10,[112][113][114][115][116][117][118][119][120][121][122][123][124][125]. Furthermore, expression of IP 3 Rs in atrial myocytes has been demonstrated at mRNA and protein levels in various organisms, including mouse, rabbit, rat and human [15,17,41,58].…”

Section: Ip 3 Signaling In Atrial Myocytesmentioning

confidence: 99%

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Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Kockskämper

Zima

Roderick

et al. 2008

Journal of Molecular and Cellular Cardiology

172

149

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Inositol 1,4,5-trisphosphate (IP 3 ) is a ubiquitous intracellular messenger regulating diverse functions in almost all mammalian cell types. It is generated by membrane receptors that couple to phospholipase C (PLC), an enzyme which liberates IP 3 from phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The major action of IP 3 , which is hydrophilic and thus translocates from the membrane into the cytoplasm, is to induce Ca 2+ release from endogenous stores through IP 3 receptors (IP 3 Rs). Cardiac excitation-contraction coupling relies largely on ryanodine receptor (RyR)-induced Ca 2+ release from the sarcoplasmic reticulum. Myocytes express a significantly larger number of RyRs compared to IP 3 Rs (∼100:1), and furthermore they experience substantial fluxes of Ca 2+ with each heartbeat. Therefore, the role of IP 3 and IP 3 -mediated Ca 2+ signaling in cardiac myocytes has long been enigmatic. Recent evidence, however, indicates that despite their paucity cardiac IP 3 Rs may play crucial roles in regulating diverse cardiac functions. Strategic localization of IP 3 Rs in cytoplasmic compartments and the nucleus enables them to participate in subsarcolemmal, bulk cytoplasmic and nuclear Ca 2+ signaling in embryonic stem cell-derived and neonatal cardiomyocytes, and in adult cardiac myocytes from the atria and ventricles. Intriguingly, expression of both IP 3 Rs and membrane receptors that couple to PLC/IP 3 signaling is altered in cardiac disease such as atrial fibrillation or heart failure, suggesting the involvement of IP 3 signaling in the pathology of these diseases. Thus, IP 3 exerts important physiological and pathological functions in the heart, ranging from the regulation of pacemaking, excitation-contraction and excitation-transcription coupling to the initiation and/or progression of arrhythmias, hypertrophy and heart failure. KeywordsInositol 1,4,5-trisphosphate; Cardiac myocyte; Calcium; Inotropy; Arrhythmias; Nucleus; Hypertrophy © 2008 Elsevier Inc. All rights reserved. * Corresponding author. E-mail address: jens.kockskaemper@meduni-graz.at (J. Kockskämper).. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript The discovery of IP 3A quarter of a century ago it was shown that D-myo inositol 1,4,5-trisphosphate (IP 3 ) releases Ca 2+ from a non-mitochondrial internal Ca 2+ store [1]. Since this hallmark discovery, IP 3 has emerged as a ubiquitous intracellular messenger, releasing Ca 2+ from stores through activation of IP 3 receptors (IP 3 Rs) in almost all eukaryotic cells. The major IP 3 -sensitive intracellular Ca 2+ store is the endoplasmic reticulum. However, IP 3 has also been shown to release Ca 2+ stored in other compartments, such as the Golgi and the nuclear envelope [2]. In addition, IP 3 Rs are present on the plasma membrane of some cell types, where they can gate Ca 2+ influx [3]. A crucial role for IP 3 -dependent Ca 2+ release has been demonstrated in many mammalian cell types, ranging from tiny platelets, where it initiates blood clottin...

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Section: Ip 3 Signaling In Atrial Myocytesmentioning

confidence: 91%

Section: Ip 3 Signaling In Atrial Myocytesmentioning

confidence: 99%

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Kockskämper

Zima

Roderick

et al. 2008

Journal of Molecular and Cellular Cardiology

172

149

View full text Add to dashboard Cite

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“…6) The cardiac stimulatory effects of 5-HT in the heart 7) were similarly attributed to the 5-HT 2 receptors present in cardiomyocytes.…”

Section: )mentioning

confidence: 98%

“…6) The cardiac stimulatory effects of 5-HT in the heart 7) were similarly attributed to the 5-HT 2 receptors present in cardiomyocytes. 8) However, the role of 5-HT antagonists in myocardial ischemic cellular damage remains unclear.…”

mentioning

confidence: 98%

“…4,5) Sarpogrelate, a 5-HT 2A antagonist, was shown to have a beneficial effect on ischemia-reperfusion injury in isolated Langendorff-perfused guinea-pig hearts perfused with no-blood solution.6) The cardiac stimulatory effects of 5-HT in the heart 7) were similarly attributed to the 5-HT 2 receptors present in cardiomyocytes.8) However, the role of 5-HT antagonists in myocardial ischemic cellular damage remains unclear.The identification of factors regulating cardiomyocyte survival and growth is important to more clearly understand the pathogenesis of congenital heart diseases. Interest in the link between the signaling circuitry for external stimuli and mitochondrial apoptotic machinery in cardiac disease is increasing.…”

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confidence: 99%

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Protective Effects of Fluvoxamine against Ischemia/Reperfusion Injury in Isolated, Perfused Guinea-Pig Hearts

Muto

Usuda

Yamamura

et al. 2014

Biological & Pharmaceutical Bulletin

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Key words fluvoxamine; left ventricular developed pressure; 31 P-NMR; mitochondrial permeability transition pore (MPTP); ischemia-reperfusion injury; apoptosis Serotonin (5-hydroxytryptamine; 5-HT) is a neurohormone that has been shown to regulate cardiovascular functions. 1)Circulating 5-HT can also be taken up by sympathetic neurons and vascular endothelial cells, from which it can then be co-released.2) Previous studies reported that antagonists of 5-HT 2A may be potential therapeutic agents for hypertension as well as peripheral vascular disease, 3) and also prevented cardiac dysfunction in ischemic-reperfusion injury hearts. 4,5) Sarpogrelate, a 5-HT 2A antagonist, was shown to have a beneficial effect on ischemia-reperfusion injury in isolated Langendorff-perfused guinea-pig hearts perfused with no-blood solution.6) The cardiac stimulatory effects of 5-HT in the heart 7) were similarly attributed to the 5-HT 2 receptors present in cardiomyocytes.8) However, the role of 5-HT antagonists in myocardial ischemic cellular damage remains unclear.The identification of factors regulating cardiomyocyte survival and growth is important to more clearly understand the pathogenesis of congenital heart diseases. Interest in the link between the signaling circuitry for external stimuli and mitochondrial apoptotic machinery in cardiac disease is increasing. Mitochondria are also known to play an important role in apoptotic signaling, 9) especially in the heart. 10) In relation to our investigation of Ca 2+ systems, the effects of an increase in mitochondrial Ca 2+ ([Ca 2+ ] m ) uptake on changes in the Ca 2+ content or acidification of the perfusate, similar to the end of ischemia or reperfusion following global ischemia in hearts, was previously examined after the administration of each optical isomer of a 5-HT 1A antagonist pyrapyridolol. 11) Changes in [Ca 2+ ] m were measured to assess their contribution to injury using an opener or inhibitor of the mitochondrial permeability transition pore (MPTP). 12)The results of the present study indicate that the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Fig. 1A) may inhibit opening of the MPTP by preventing [Ca 2+ ] m overloadinduced apoptosis in ischemia-reperfusion hearts, similar to the 5-HT 1A antagonist pyrapyridolol.11) Evidence now suggests that apoptosis, or programmed cell death, is an important response of the myocardium to ischemia, which precedes cell necrosis and appears to contribute to the overall sequelae of cardiac injury.13) The molecular mechanisms of cardiac functions triggered by 5-HT have to be elucidated in detail. The role of 5-HT in this response can be delineated with 5-HT inhibitors.14) Therefore, we examined which protective action was associated with the beneficial effects of SSRI, with respect to reductions in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive myocytes and caspase-3 activity, in order to compare these effects to those of 5-HT-rela...

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Genotoxicity of naturally occurring indole compounds: correlation between covalent DNA binding and other genotoxicity tests

Reddy

Storer

Laws

et al. 2002

Environ and Mol Mutagen

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3-Methylindole (3MI), melatonin (Mel), serotonin (Ser), and tryptamine (Tryp) were evaluated in vitro for their potential to induce DNA adducts, DNA strand breaks, chromosomal aberrations (Abs), inhibition of DNA synthesis, and mutations. All compounds produced DNA adducts in calf thymus DNA in the presence of rat liver S9. In cultured rat hepatocytes, all produced DNA adducts but none induced DNA strand breaks. In Chinese hamster ovary cells, 3MI and Mel produced DNA adducts, Abs, and inhibition of DNA synthesis with and without S9, except that Mel without S9 did not form adducts. Ser formed DNA adducts, was an equivocal Abs inducer, and suppressed DNA synthesis. Tryp induced neither adducts nor Abs, but did suppress DNA synthesis with S9. Ser and Tryp were less cytotoxic than 3MI and Mel. Mel, Ser, and Tryp failed to induce mutations in Salmonella and E. coli strains with or without S9. 3MI and Mel produced DNA adducts but not mutations in Salmonella TA100 with S9. 3MI and its metabolite indole 3-carbinol also did not induce mutations in a shuttle vector system in human cells. The lack of correlation between DNA adducts and other genotoxicity endpoints for these indole compounds may be due to the higher sensitivity of the (32)P-postlabeling adduct assay or it may indicate that the indole-DNA adducts per se are not mutagenic and are not able to induce strand breaks or alkali-labile lesions. The indole-induced Abs may result from cytotoxicity and suppression of DNA synthesis with minimal if any contribution from DNA adducts.

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Receptor mechanisms involved in the 5‐HT‐induced inotropic action in the rat isolated atrium

Cited by 47 publications

References 37 publications

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Protective Effects of Fluvoxamine against Ischemia/Reperfusion Injury in Isolated, Perfused Guinea-Pig Hearts

Genotoxicity of naturally occurring indole compounds: correlation between covalent DNA binding and other genotoxicity tests

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