2. Academic Validation
  3. Cyclopiazonic acid alters serotonin-induced responses in rat thoracic aorta

Cyclopiazonic acid alters serotonin-induced responses in rat thoracic aorta

  • Vascul Pharmacol. 2014 May-Jun;61(2-3):43-8. doi: 10.1016/j.vph.2014.03.008.
C Selli 1,  Y Erac 2,  M Tosun 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, Faculty of Pharmacy, Ege University, 35100, Izmir, Turkey. Electronic address: cigdem.selli@ege.edu.tr.
  • 2 Department of Pharmacology, Faculty of Pharmacy, Ege University, 35100, Izmir, Turkey.
PMID: 24704610 DOI: 10.1016/j.vph.2014.03.008
Abstract

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.

Keywords

Caveolae; Methysergide; Receptor internalization.

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