Word R A, Casey M L, Kamm K E, Stull J T
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235.
Am J Physiol. 1991 Apr;260(4 Pt 1):C861-7. doi: 10.1152/ajpcell.1991.260.4.C861.
Adenosine 3',5'-cyclic monophosphate (cAMP) is believed to be an important mediator of myometrial relaxation, and there is evidence to suggest that guanosine 3',5'-cyclic monophosphate (cGMP) is a mediator of smooth muscle relaxation in vascular and probably nonvascular tissues. To investigate the biochemical mechanisms involved in regulation of human myometrial contractility, we studied the effects of analogues of cAMP and cGMP, as well as activators of adenylate and guanylate cyclases, on uterine smooth muscle contractile activity. We found that myometrial smooth muscle cells in culture respond to analogues of cGMP and cAMP, as well as activators of guanylate cyclase, with a significant decrease in the resting and endothelin-induced increase in [Ca2+]i. Treatment of human uterine smooth muscle strips with sodium nitroprusside or isoproterenol results in diminished force and frequency of contraction as well as a decrease in the rate and extent of myosin light chain phosphorylation in spontaneous contractions of human myometrium. cGMP did not effect relaxation of endothelin-stimulated contractions of human myometrium, but the relaxation effects of cGMP were dramatic in precontracted bovine tracheal and human fetal aortic smooth muscles. Whereas cGMP and cAMP act to promote a decrease in the force and frequency of spontaneous contractions in human myometrium, this tissue is not as responsive to the actions of cyclic nucleotides as are other types of smooth muscle.
3',5'-环磷酸腺苷（cAMP）被认为是子宫肌层舒张的重要介质，并且有证据表明3',5'-环磷酸鸟苷（cGMP）是血管及可能的非血管组织中平滑肌舒张的介质。为了研究参与调节人子宫肌层收缩性的生化机制，我们研究了cAMP和cGMP类似物以及腺苷酸环化酶和鸟苷酸环化酶激活剂对子宫平滑肌收缩活性的影响。我们发现，培养的子宫肌层平滑肌细胞对cGMP和cAMP类似物以及鸟苷酸环化酶激活剂有反应，静息状态下以及内皮素诱导的细胞内钙离子浓度（[Ca2+]i）升高均显著降低。用硝普钠或异丙肾上腺素处理人子宫平滑肌条，会导致收缩力和频率降低，以及人子宫肌层自发收缩中肌球蛋白轻链磷酸化的速率和程度下降。cGMP对人子宫肌层内皮素刺激的收缩没有舒张作用，但cGMP对预先收缩的牛气管和人胎儿主动脉平滑肌的舒张作用显著。虽然cGMP和cAMP可促进人子宫肌层自发收缩的力和频率降低，但该组织对环核苷酸作用的反应不如其他类型的平滑肌敏感。
