Arkinstall S J, Jones C T
Laboratory of Cellular and Developmental Physiology, University of Oxford, John Radcliffe Hospital, Headington.
J Endocrinol. 1990 Oct;127(1):15-21. doi: 10.1677/joe.0.1270015.
The regulatory factors controlling uterine activity during pregnancy remain unclear in many species. Since myometrial relaxants raise intracellular cyclic AMP, modulation of signalling pathways coupling cell-surface receptors to adenylate cyclase activation could be an important site for control. To assess the functional activity of the stimulatory GTP-binding protein Gs we have measured adenylate cyclase activation by GTP, its non-hydrolysable analogue guanosine 5'-(beta-gamma-imido)triphosphate (Gpp(NH)p), fluoride, forskolin and manganese in a 50,000 g membrane fraction prepared from the myometrium of non-pregnant, mid-pregnant (30-32 days) and late-pregnant (62-66 days) guinea-pigs (full term 67 +/- 2 days). While forskolin- and manganese-dependent enzyme activation was unaltered by pregnancy, maximal stimulation by Gpp(NH)p and fluoride was enhanced by up to 200%. Recovery of adenylate cyclase activity in the 50,000 g fraction was essentially constant at 20-24% of the total activity throughout pregnancy, and thus cannot explain the increases observed. Since guanine nucleotides and fluoride stimulate adenylate cyclase through activating Gs, and forskolin and manganese act at the level of the catalytic unit, these data are consistent with a pregnancy-related increase in Gs functional coupling while adenylate cyclase activity is unaltered. These observations suggest a physiological regulation of myometrial Gs activity during pregnancy which could facilitate hormonal stimulation of adenylate cyclase and contribute to uterine quiescence by increasing uterine sensitivity to relaxants.
在许多物种中，孕期控制子宫活动的调节因子仍不明确。由于子宫肌层舒张剂可提高细胞内的环磷酸腺苷（cAMP）水平，因此，调节将细胞表面受体与腺苷酸环化酶激活相偶联的信号通路可能是一个重要的控制位点。为了评估刺激性GTP结合蛋白Gs的功能活性，我们在从非妊娠、妊娠中期（30 - 32天）和妊娠晚期（62 - 66天）豚鼠（足月为67±2天）子宫肌层制备的50,000g膜组分中，测定了GTP、其不可水解类似物鸟苷5'-（β，γ-亚氨基）三磷酸（Gpp(NH)p）、氟化物、福斯可林和锰对腺苷酸环化酶的激活作用。虽然福斯可林和锰依赖性的酶激活不受妊娠影响，但Gpp(NH)p和氟化物的最大刺激作用增强了高达200%。在整个孕期，50,000g组分中腺苷酸环化酶活性的恢复基本保持在总活性的20 - 24%不变，因此无法解释所观察到的增加情况。由于鸟嘌呤核苷酸和氟化物通过激活Gs刺激腺苷酸环化酶，而福斯可林和锰作用于催化单位水平，这些数据与妊娠相关的Gs功能偶联增加一致，而腺苷酸环化酶活性未改变。这些观察结果提示孕期子宫肌层Gs活性存在生理调节，这可能促进激素对腺苷酸环化酶的刺激，并通过增加子宫对舒张剂的敏感性来促进子宫静止。
