Attenuation of the serotonin-induced increase in intracellular calcium in rat aortic smooth muscle cells by sarpogrelate.
Although serotonin (5-HT) induced proliferation of vascular smooth muscle cells is considered to involve changes in intracellular Ca2+ ([Ca2+]i), the mechanism of Ca2+ mobilization by 5-HT is not well defined. In this study, we examined the effect of 5-HT on rat aortic smooth muscle cells (RASMCs) by Fura-2 microfluorometry for [Ca2+]i measurements. 5-HT was observed to increase the [Ca2+]i in a concentration- and time-dependent manner. This action of 5-HT was dependent upon the extracellular concentration of Ca2+ ([Ca2+]e) and was inhibited by both Ca2+ channel antagonists (verapamil and diltiazem) and inhibitors of sarcoplasmic reticular Ca2+ pumps (thapsigargin and cyclopia zonic acid). The 5-HT-induced increase in [Ca2+]i was blocked by sarpogrelate, a 5-HT2A-receptor antagonist, but not by different agents known to block other receptor sites. 5-HT-receptor antagonists such as ketanserin, cinanserin, and mianserin, unlike methysergide, were also found to inhibit the 5-HT-induced Ca2+ mobilization, but these agents were less effective in comparison to sarpogrelate. On the other hand, the increase in [Ca2+]i in RASMCs by ATP, angiotensin II, endothelin-1, or phorbol ester was not affected by sarpogrelate. These results indicate that Ca2+ mobilization in RASMCs by 5-HT is mediated through the activation of 5-HT2A receptors and support the view that the 5-HT-induced increase in [Ca2+]i involves both the extracellular and intracellular sources of Ca2+.
Saini
Harjot K
HK
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Sharma
Sushil K
SK
Zahradka
Peter
P
Kumamoto
Hideo
H
Takeda
Nobuakira
N
Dhalla
Naranjan S
NS
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*
D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin; D002118:Calcium