Cyclopiazonic acid alters serotonin-induced responses in rat thoracic aorta


SELLI C., ERAÇ Y. , TOSUN M.

VASCULAR PHARMACOLOGY, cilt.61, ss.43-48, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 61
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.vph.2014.03.008
  • Dergi Adı: VASCULAR PHARMACOLOGY
  • Sayfa Sayısı: ss.43-48

Özet

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, alpha(1)-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. (C) 2014 Elsevier Inc All rights reserved.