Inhibitory effect of Pyr6 (an Orai channel blocker) on agonist-induced contractions in rat uterus
| Autor: | Francisco das Chagas Cardoso Filho, Paulo Marques da Silva Cavalcanti, Ícaro Araújo de Sousa, Suzana Maria Pereira Galvão Cavalcanti, Joubert Aires de Sousa, Pablo Queiroz Lopes, Gabriel Medina Sobreira de Meneses, José Victor Miranda Cardoso |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Agonist
medicine.medical_specialty Carbachol medicine.drug_class Oxytocin chemistry.chemical_compound Transient receptor potential channel Uterine Contraction Pregnancy Internal medicine Medicine Animals Channel blocker TRPC business.industry Myometrium Obstetrics and Gynecology Rats Endocrinology chemistry Female business Cyclopiazonic acid medicine.drug |
| Zdroj: | The journal of obstetrics and gynaecology researchReferences. 47(12) |
| ISSN: | 1447-0756 |
| Popis: | AIM Both human and rat myometrium express stromal interaction molecule (STIM) and Orai/transient receptor potential canonical (TRPC) proteins, which are components of plasma membrane Ca2+ store-operated channels. There are reports that these proteins mediate agonist-induced Ca2+ influx in cultured myometrial cells. In this study, we aimed to determine the effects of Pyr6, an Orai channel blocker, on different agonist-induced contractions in isolated segments of rat uterus. MAIN FINDINGS In Ca2+ -free Tyrode's solution, Pyr6 (3 μM) promoted a reduction in both the magnitude and frequency of Ca2+ (1 mM)-induced uterine contractions after the addition of carbachol (CCh, 100 μM), but not after the addition of oxytocin (OT, 150 nM). In Ca2+ (0.18 mM)-Tyrode's solution, Pyr6 completely relaxed uterine contractions induced by both CCh and cloprostenol (300 nM), but not those induced by either KCI (40-80 mM) or OT. The addition of Pyr6 abolished the oscillatory uterine contractions induced by Ca2+ after the addition of cyclopiazonic acid (CPA, 10 μM). When pre-incubated (5 min), Pyr6 reduced the magnitude of both CCh-induced phasic and tonic contractions. The addition of Pyr2 (3 μM), an Orai and TRPC channel blocker, abolished uterine contractions induced by CCh or OT. CONCLUSION Considering Pyr6 as an Orai channel blocker and its inhibitory effect on uterine contractions induced by CCh, CPA, and cloprostenol, we suggest that Orai channels are required for the maintenance of contractions induced by these agonists in rat uterus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text