Naghashpour M, Dahl G
Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33101, USA.
Biol Reprod. 2000 Nov;63(5):1421-7. doi: 10.1095/biolreprod63.5.1421.
Calcitonin gene-related peptide (CGRP) inhibits myometrial contractile activity. However, the responsiveness of the mouse myometrium to CGRP is dependent on the hormonal and gestational stage. The inhibitory effect of CGRP in the myometrium is prominent during gestation and declines at parturition. The present study was undertaken to examine if nitric oxide (NO) production by nitric oxide synthase (NOS) isoforms mediates the inhibitory action of CGRP on uterine contractions as has been suggested earlier. Transgenic mice deficient in either of the three major NOS isoforms: endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were used. Isometric force measurements on myometrial strips obtained from NOS-deficient mice were carried out and the inhibitory capacity of CGRP was monitored. CGRP inhibited KCl-induced contractions of the myometrial strips obtained from eNOS(-/-), iNOS(-/-), and nNOS(-/-) mice with equal efficiency as in wild-type animals. Additionally, NOS protein expression in the mouse uterus during gestation and during the estrous cycle was examined by means of Western immunoblot analysis. No correlation between NOS expression and inhibitory activity of CGRP was evident. The results suggest that the inhibitory action of CGRP in the mouse uterus is independent of the activity of these NOS isoforms.
降钙素基因相关肽（CGRP）可抑制子宫肌层的收缩活性。然而，小鼠子宫肌层对CGRP的反应性取决于激素水平和妊娠阶段。CGRP对子宫肌层的抑制作用在妊娠期较为显著，而在分娩时减弱。本研究旨在检验一氧化氮合酶（NOS）同工型产生的一氧化氮（NO）是否如先前所提示的那样介导CGRP对子宫收缩的抑制作用。使用了缺乏三种主要NOS同工型之一的转基因小鼠，即内皮型NOS（eNOS）、诱导型NOS（iNOS）和神经元型NOS（nNOS）。对从NOS缺陷小鼠获得的子宫肌条进行等长力测量，并监测CGRP的抑制能力。CGRP对从eNOS（-/-）、iNOS（-/-）和nNOS（-/-）小鼠获得的子宫肌条的KCl诱导收缩的抑制效率与野生型动物相同。此外，通过蛋白质免疫印迹分析检测了小鼠子宫在妊娠期和发情周期中的NOS蛋白表达。未发现NOS表达与CGRP抑制活性之间存在明显相关性。结果表明，CGRP在小鼠子宫中的抑制作用独立于这些NOS同工型的活性。
