Attenuation of the serotonin-induced increase in intracellular calcium in rat aortic smooth muscle cells by sarpogrelate

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Date
2003-11-30
Authors
Saini, HK
Sharma, SK
Zahradka, P
Kumamoto, H
Takeda, N
Dhalla, NS
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Abstract
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 cyclopiazonic 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+.
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Keywords
sarpogrelate, serotonin, vascular smooth muscle cells, intracellular Ca2+, PROTEIN-KINASE-C, ANGIOTENSIN-II, DNA-SYNTHESIS, RECEPTOR ANTAGONIST, ANTIPLATELET AGENT, PROLIFERATION; 5-HYDROXYTRYPTAMINE, EXPRESSION, MECHANISMS, ARTERIES
Citation
0008-4212; CAN J PHYSIOL PHARMACOL, NOV 2003, vol. 81, no. 11, p.1056 to 1063.