Cyclopiazonic acid alters serotonin-induced responses in rat thoracic aorta.
We previously showed that endothelin A (ETA) receptor antagonist BQ-123 partially inhibited cyclopiazonic acid (CPA)-enhanced endothelin-1 (ET-1)-induced contractions suggesting enhancement of ETA receptor internalization in caveolar structures by sarco/endoplasmic reticulum Ca+2 ATPase (SERCA) blockade. Since serotonin (5-Hydroxytryptamine, 5-HT) receptors are reported to be localized on caveolar membranes, we investigated whether SERCA inhibition affects 5-HT-induced responses and 5-HT receptor antagonism. For this purpose, vascular responses were measured in thoracic aorta segments from male Wistar albino rats using isolated tissue experiments. Data showed that CPA inhibits 5-HT- and PE-induced contractions in intact vessels while potentiating those in endothelium-denuded. Furthermore, non-selective 5-HT receptor blocker methysergide partially inhibited CPA-induced 5-HT contractions. However, α1-adrenergic receptor antagonist prazosin totally inhibited CPA-potentiated PE contractions. We suggest that SERCA inhibition results in 5-HT receptor internalization similar to ETA receptors possibly through protein kinase C activation by increased subsarcolemmal Ca2+ levels, eventually preventing 5-HT receptor antagonism.
Department of Pharmacology, Faculty of Pharmacy, Ege University, 35100, Izmir, Turkey. Electronic address: cigdem.selli@ege.edu.tr.
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Selli
Department of Pharmacology, Faculty of Pharmacy, Ege University, 35100, Izmir, Turkey.
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Erac
Department of Pharmacology, Faculty of Pharmacy, Ege University, 35100, Izmir, Turkey.
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Tosun
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D007211:Indoles; D011985:Receptors, Serotonin; D014665:Vasodilator Agents; D010656:Phenylephrine; D012701:Serotonin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C000543:cyclopiazonic acid; D011224:Prazosin; D008784:Methysergide
Caveolae; Methysergide; Receptor internalization