Cao Chunhua, Han Jeong Hee, Kim Sung Zoo, Cho Kyung Woo, Kim Suhn Hee
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.
Cardiovasc Res. 2003 Aug 1;59(2):360-8. doi: 10.1016/s0008-6363(03)00394-8.
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.
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.
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.
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.
血清素（5-羟色胺[5-HT]）受体存在于外周组织以及中枢神经系统中。血清素受体介导心房的正性肌力和变时作用。本研究的目的是探讨内源性血清素对心房利钠肽（ANP）从心房分泌的调节作用的生理机制。
使用离体灌注的非搏动大鼠心房模型。测量因心房内压升高引起的心房容积变化。通过放射免疫分析法测量ANP的浓度，通过[3H]-菊粉清除率测量细胞外液（ECF）的转运。
内源性5-HT受体激动剂血清素引起牵张诱导的ANP分泌的浓度依赖性抑制，但其抑制作用不如5-HT(2)受体选择性激动剂马来酸α-甲基-5-HT明显。血清素和马来酸α-甲基-5-HT对牵张诱导的ANP分泌的抑制作用被5-HT(2)受体拮抗剂酮色林减弱，而被5-HT(4)受体拮抗剂RS23597-190增强。血清素对ANP分泌的抑制作用被新霉素、星形孢菌素和白屈菜红碱减弱。相反，5-HT(4)受体选择性激动剂2-[1-(4-胡椒基)哌嗪基]苯并噻唑引起牵张诱导的ANP分泌增强，该作用被RS23597-190和盐酸SB203186完全阻断，但不被酮色林阻断。此作用不受MDL12330、KT-5720或H-89影响。血清素以及5-HT(2)或5-HT(4)受体激动剂对单个心房肌细胞内的Ca(2+)浓度无影响。
这些结果表明，心房5-HT(2)和5-HT(4)受体激动剂对ANP分泌的调节作用相反，血清素对ANP分泌的抑制作用可能通过5-HT(2)受体和磷脂酶C途径发挥作用。
