title: Effects of cyclopiazonic acid and dexamethasone on serotonin-induced calcium responses in vascular smooth muscle cells.
abstract: We previously observed that sarcoendoplasmic reticulum Ca(2+) 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 Ca(2+) responses along with attenuating the receptor antagonism by store-operated Ca(2+) (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 Ca(2+) 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 Ca(2+) elevations. Ketanserin partially decreased 5-HT-induced and CPA-potentiated Ca(2+) 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 Ca(2+) elevations in the presence of SERCA inhibition is induced by SOC entry and PKC activation.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Ege University, 35040, Izmir, Turkey. cigdemselli@gmail.com.|Applied Bioinformatics of Cancer, Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, Edinburgh, EH4 2XU, UK. cigdemselli@gmail.com.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Selli
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Ege University, 35040, Izmir, Turkey.
authors.forename: Metiner
authors.initials: M
authors.lastname: Tosun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012701:Serotonin / Q000737:chemistry / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin; D003907:Dexamethasone; D007650:Ketanserin; D011493:Protein Kinase C; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C000543:cyclopiazonic acid; D008784:Methysergide
keywords: CPA; Dexamethasone; PKC; SOC; Serotonin