Zhuge R, Li S, Chen T H, Hsu W H
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011, USA.
Mol Reprod Dev. 1995 May;41(1):20-8. doi: 10.1002/mrd.1080410105.
This study investigated the underlying mechanisms of oxytocin (OT)-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in acutely dispersed myometrial cells from prepartum sows. A dose-dependent increase in [Ca2+]i was induced by OT (0.1 nM to 1 microM) in the presence and absence of extracellular Ca2+ ([Ca2+]e). [Ca2+]i was elevated by OT in a biphasic pattern, with a spike followed by a sustained plateau in the presence of [Ca2+]e. However, in the absence of [Ca2+]e, the [Ca2+]i response to OT became monophasic with a lower amplitude and no plateau, and this monophasic increase was abolished by pretreatment with ionomycin, a Ca2+ ionophore. Administration of OT (1 microM) for 15 sec increased inositol 1,4,5-trisphosphate (IP3) formation by 61%. Pretreatment with pertussis toxin (PTX, 1 microgram/ml) for 2 hr failed to alter the OT-induced increase in [Ca2+]i and IP3 formation. U-73122 (30 nM to 3 microM), a phospholipase C (PLC) inhibitor, depressed the rise in [Ca2+]i by OT dose dependently. U-73122 (3 microM) also abolished the OT-induced IP3 formation. Thapsigargin (2 microM), an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum, did not increase [Ca2+]i. However, it did time-dependently inhibit the OT-induced increase in [Ca2+]i. Nimodipine (1 microM), a voltage-dependent Ca2+ channel (VDCC) blocker, inhibited the OT-induced plateau by 26%. La3+ (1 mM), a nonspecific Ca2+ channel blocker, abrogated the OT-induced plateau. In whole-cell patch-clamp studies used to evaluate VDCC activities, OT (0.1 microM) increased Ca2+ current (ICa) by 40% with no apparent changes in the current-voltage relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究调查了催产素（OT）诱导产前母猪急性分离的子宫肌层细胞内钙离子浓度（[Ca2+]i）升高的潜在机制。在存在和不存在细胞外钙离子（[Ca2+]e）的情况下，OT（0.1 nM至1 microM）均可诱导[Ca2+]i呈剂量依赖性增加。在存在[Ca2+]e的情况下，OT使[Ca2+]i以双相模式升高，先是出现一个峰值，随后是一个持续的平台期。然而，在不存在[Ca2+]e的情况下，[Ca2+]i对OT的反应变为单相，幅度较低且无平台期，这种单相增加可被钙离子载体离子霉素预处理所消除。给予OT（1 microM）15秒可使肌醇1,4,5-三磷酸（IP3）生成增加61%。用百日咳毒素（PTX，1微克/毫升）预处理2小时未能改变OT诱导的[Ca2+]i升高和IP3生成。磷脂酶C（PLC）抑制剂U-73122（30 nM至3 microM）可剂量依赖性地抑制OT诱导的[Ca2+]i升高。U-73122（3 microM）也可消除OT诱导的IP3生成。内质网中Ca(2+)-ATP酶抑制剂毒胡萝卜素（2 microM）不会增加[Ca2+]i。然而，它确实会时间依赖性地抑制OT诱导的[Ca2+]i升高。电压依赖性钙离子通道（VDCC）阻滞剂尼莫地平（1 microM）可使OT诱导的平台期降低26%。非特异性钙离子通道阻滞剂La3+（1 mM）可消除OT诱导的平台期。在用于评估VDCC活性的全细胞膜片钳研究中，OT（0.1 microM）可使钙离子电流（ICa）增加40%，电流-电压关系无明显变化。（摘要截取自250字）
