Diverse regulation of atrial natriuretic peptide secretion by serotonin receptor subtypes.
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-HT(2) 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-HT(2) receptor antagonist, and accentuated by RS23597-190, a 5-HT(4) 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-HT(4) 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 Ca(2+) concentration in single atrial myocytes was not changed by serotonin and agonist for either 5-HT(2) or 5-HT(4) receptor.


CONCLUSIONS
These results suggest that atrial 5-HT(2) and 5-HT(4) 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-HT(2) receptor and phospholipase C pathway.
Cao
Chunhua
C
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.
Han
Jeong Hee
JH
Kim
Sung Zoo
SZ
Cho
Kyung Woo
KW
Kim
Suhn Hee
SH
D000067956:Adenylyl Cyclase Inhibitors; D000470:Alkaloids; D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D053119:Benzophenanthridines; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000378:metabolism*; D006325:Heart Atria; D007097:Imines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology; D010477:Perfusion; D010617:Phenanthridines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides; D013844:Thiazoles / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D062366:para-Aminobenzoates
C084177:3-(piperidine-1-yl)propyl 4-amino-5-chloro-2-methoxybenzoate hydrochloride; D000067956:Adenylyl Cyclase Inhibitors; D000470:Alkaloids; D062365:Aminobenzoates; D053119:Benzophenanthridines; D052160:Benzothiazoles; D002227:Carbazoles; D007097:Imines; D007211:Indoles; D007546:Isoquinolines; D010617:Phenanthridines; D010879:Piperazines; D010880:Piperidines; D011758:Pyrroles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D013844:Thiazoles; D062366:para-Aminobenzoates; C087141:2-(1-(4-piperonyl)piperazinyl)benzothiazole; D044422:Receptors, Serotonin, 5-HT4; C042390:alpha-methylserotonin; D012701:Serotonin; C057416:KT 5720; C014925:RMI 12330A; D009320:Atrial Natriuretic Factor; D007650:Ketanserin; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019311:Staurosporine; D009355:Neomycin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium