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Cardiovascular Research 2003 59(2):360-368; doi:10.1016/S0008-6363(03)00394-8
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Diverse regulation of atrial natriuretic peptide secretion by serotonin receptor subtypes

Chunhua Cao, Jeong Hee Han, Sung Zoo Kim, Kyung Woo Cho and Suhn Hee Kim*

Department of Physiology, Institute for Medical Sciences and Basic Research Institute, Chonbuk National University Medical School, 2-20 Keum-Am-Dong-San, Jeonju 561-180, South Korea

* Corresponding author. Tel.: +82-63-274-9788; fax: +82-63-274-9892. shkim{at}moak.chonbuk.ac.kr

Objective: Serotonin (5-hydroxytryptamine [5-HT]) receptors are located in peripheral tissues as well as in the central nervous system. Serotonin receptors mediate positive inotropic and chronotropic effects in atria. The aim of this study was to investigate physiological role of endogenous serotonin on the regulation of atrial natriuretic peptide (ANP) secretion from the atria. Methods: An isolated perfused nonbeating rat atrial model was used. Changes in atrial volume induced by increasing intra-atrial pressure were measured. The concentration of ANP was measured by radioimmunoassay and the translocation of ECF was measured by [3H]-inulin clearance. Results: Serotonin, an endogenous 5-HT receptor agonist, caused concentration-dependent suppressions of stretch-induced ANP secretion, which were less pronounced than those caused by {alpha}-methyl-5-HT maleate, a 5-HT2 receptor selective agonist. The suppression of stretch-induced ANP secretion due to serotonin and {alpha}-methyl-5-HT maleate was attenuated by ketanserin, a 5-HT2 receptor antagonist, and accentuated by RS23597-190, a 5-HT4 receptor antagonist. The suppressive effect of serotonin on ANP secretion was attenuated by neomycin, staurosporine, and chelerythrine. In contrast, 2-[1-(4-piperonyl)piperazinyl]benzothiazole, a 5-HT4 receptor selective agonist, caused an accentuation of stretch-induced ANP secretion, which was completely blocked by RS23597-190 and SB203186 HCl but not by ketanserin. This effect was not affected by MDL12330, KT-5720, or H-89. The intracellular Ca2+ concentration in single atrial myocytes was not changed by serotonin and agonist for either 5-HT2 or 5-HT4 receptor. Conclusions: These results suggest that atrial 5-HT2 and 5-HT4 receptor agonists have opposite actions on the regulation of ANP secretion and the suppressive effect of serotonin on the ANP secretion may act through 5-HT2 receptor and phospholipase C pathway.

KEYWORDS Atrial function; Calcium; Inotropic agents; Natriuretic peptide; Receptor; Serotonin


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