Effects of cyclopiazonic acid and dexamethasone on serotonin-induced calcium responses in vascular smooth muscle cells


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Selli C. , TOSUN M.

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, cilt.72, ss.245-253, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 72 Konu: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1007/s13105-016-0474-8
  • Dergi Adı: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
  • Sayfa Sayıları: ss.245-253

Özet

We previously observed that sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) blockade by cyclopiazonic acid (CPA) significantly potentiates serotonin (5-hydroxytryptamine (5-HT))-induced vascular contractions. Furthermore, 5-HT receptor antagonist methysergide partially inhibited CPA-potentiated 5-HT contractions. In the present study, we further investigated whether SERCA inhibition potentiates 5-HT-induced Ca2+ responses along with attenuating the receptor antagonism by store-operated Ca2+ (SOC) entry and protein kinase C (PKC)-mediated mechanisms. The effects of dexamethasone that was previously shown to induce SOC entry and enhance 5-HT responses were also tested. For this purpose, intracellular Ca2+ levels were monitored in A7r5 embryonic rat vascular smooth muscle cells by spectrofluorometry using the fluorescent indicator fura-2. The results showed that CPA, although not dexamethasone, significantly potentiated 5-HT-induced Ca2+ elevations. Ketanserin partially decreased 5-HT-induced and CPA-potentiated Ca2+ elevations whereas both PKC inhibitor D-sphingosine and SOC entry blocker 2-aminoethoxydiphenyl borate (2-APB) abolished the remaining responses. The data suggests that diminished antagonistic effect on 5-HT-induced Ca2+ elevations in the presence of SERCA inhibition is induced by SOC entry and PKC activation.