Regulation of Murine Myometrial Contraction by Ginger Extract Via Activation of Voltage Dependent Ca2+ Channels

Abstract

Voltage-dependent L-type Ca 2+ channel (VDCC L ) and T-type Ca 2+ channel (VDCC T ) in murine myometrium was identified in murine myometrium. Its regulatory functions were characterized by using extracts of ginger. Methanol extract of ginger was used to obtain dichloromethane fraction (Gin C). Spontaneous uterine contractions were enhanced by BayK 8644, a VDCC L activator. However, such effects were inhibited by nifedipine (a VDCC L blocker) and mibefradil (a VDCC T blocker). Mibefradil also inhibited oxytocin (OXT), prostaglandins F 2a (PGF 2a ), and prostaglandins E 2 (PGE 2 )-induced contractions. However, application of BayK 8644 in the presence of mibefradil recovered those contractions in a nifedipine-sensitive manner. These results suggest that both VDCC L and VDCC T are important in the regulation of murine myometrial contractions. Gin C (200 mg/mL) completely inhibited spontaneous contractions of murine uterus reversibly. The inhibition by Gin C on spontaneous contractions independent of L-NAME, K + channel blockers, and nerve blockers. High K + (50 mM)-induced contraction in the presence and absence of cyclopizonic acid (CPA) was also completely inhibited by Gin C, respectively. In addition, Gin C inhibited oxytocin (OXT; 10 nM)-induced contraction independent of L-NAME and blockers of protein kinases. Prostaglandin F 2a (PGF 2a )-and acetylcholine (ACh) produced contractions were also inhibited by Gin C. These results raise the possibility that Ginger extracts C inhibits spontaneous, high K + -, OXT-, PGF 2aand ACh-induced contractions by inhibition of VDCC L in mouse uterine longitudinal smooth muscle.