Ruzycky A L, Crankshaw D J
Department of Medicine, Harvard Medical School, Beth Israel Hospital, Boston, MA 02215.
Can J Physiol Pharmacol. 1988 Jan;66(1):10-7. doi: 10.1139/y88-002.
The role of inositol phospholipid (IP) hydrolysis in agonist-mediated contractility was examined in rat uterine smooth muscle by comparing carbachol-, oxytocin-, and PGF2 alpha-mediated [3H]IP accumulation and tension generation. In both estrogen- and progesterone-dominated uteri, all three agonists exhibited dose-dependent contractile responses. Agonist potencies (EC50 values) for eliciting [3H]IP accumulation or contractile responses were found to be very similar and did not change significantly between hormonal states. Maximal responses of agonist-mediated [3H]IP accumulation and tension generation were significantly affected by the endocrine state of the uterus and were dependent on the agonist examined. Maximal carbachol- and PGF2 alpha-induced [3H]IP accumulation were found to be elevated in estrogen-dominated relative to progesterone-dominated uteri, whereas maximal forces generated by these two agonists were smaller in progesterone-dominated relative to estrogen-dominated tissues. Oxytocin-induced responses did not differ between hormonal states. To determine whether these differences between [3H]IP accumulation and contractility responses could be attributed to changes in receptor-mediated signal transduction mechanisms, receptor expression and coupling to phospholipase C were studied. Myometrial muscarinic and oxytocin receptors assessed by radioligand binding were found to have three- to four-fold greater capacities in estrogen-dominated than in progesterone-dominated uteri without significant changes in agonist affinities. Agonist-mediated [3H]IP accumulation was potently inhibited by both pertussis and cholera toxins in both hormonal states. These experiments show that estrogen- and progesterone-dominated environments regulate both uterine excitability and contractility and that the mechanisms of this regulation are complex and dependent on the agonist system stimulated.
通过比较卡巴胆碱、催产素和前列腺素F2α介导的[3H]肌醇磷脂（IP）积累和张力产生，研究了IP水解在大鼠子宫平滑肌激动剂介导的收缩性中的作用。在雌激素和孕激素主导的子宫中，所有三种激动剂均表现出剂量依赖性收缩反应。发现引发[3H]IP积累或收缩反应的激动剂效力（EC50值）非常相似，并且在激素状态之间没有显著变化。激动剂介导的[3H]IP积累和张力产生的最大反应受子宫内分泌状态的显著影响，并取决于所检测的激动剂。发现相对于孕激素主导的子宫，雌激素主导的子宫中卡巴胆碱和前列腺素F2α诱导的最大[3H]IP积累升高，而相对于雌激素主导的组织，这两种激动剂在孕激素主导的子宫中产生的最大力量较小。催产素诱导的反应在激素状态之间没有差异。为了确定[3H]IP积累和收缩反应之间的这些差异是否可归因于受体介导的信号转导机制的变化，研究了受体表达和与磷脂酶C的偶联。通过放射性配体结合评估的子宫肌层毒蕈碱和催产素受体在雌激素主导的子宫中的容量比在孕激素主导的子宫中大三至四倍，而激动剂亲和力没有显著变化。在两种激素状态下，百日咳毒素和霍乱毒素均能有效抑制激动剂介导的[3H]IP积累。这些实验表明，雌激素和孕激素主导的环境调节子宫的兴奋性和收缩性，并且这种调节机制复杂且取决于所刺激的激动剂系统。
