Yanagita T, Yamamoto R, Sugano T, Kobayashi H, Uezono Y, Yokoo H, Shiraishi S, Minami S I, Wada A
Department of Pharmacology, Miyazaki Medical College, Miyazaki 889-1692, Japan.
Br J Pharmacol. 2000 Aug;130(8):1727-30. doi: 10.1038/sj.bjp.0703500.
In isolated rat uterine strips, adrenomedullin (AM) inhibited the spontaneous periodic contraction in a concentration-dependent manner (IC(50)=22.3+/-0.7 nM). The inhibitory effect of AM was prevented by either AM(22-52), a putative antagonist for AM receptors, or calcitonin gene-related peptide (CGRP)(8-37), a putative antagonist for CGRP receptors. AM also attenuated bradykinin (BK)-induced periodic uterine contraction, which was blocked by AM(22-52) or CGRP(8-37), whereas AM had no effect on the periodic contraction caused by oxytocin or prostaglandin F(2alpha) (PGF(2alpha)). RT-PCR analysis showed that mRNAs for calcitonin receptor-like receptor (CRLR), receptor-activity-modifying protein (RAMP)1, RAMP2 and RAMP3 were expressed in the rat uterus. These results demonstrate that AM selectively inhibits spontaneous and BK-induced periodic contraction via activating receptors for AM and CGRP.
在离体大鼠子宫肌条中,肾上腺髓质素(AM)以浓度依赖性方式抑制自发性周期性收缩(半数抑制浓度[IC(50)] = 22.3±0.7 nM)。AM的抑制作用可被AM受体的假定拮抗剂AM(22 - 52)或降钙素基因相关肽(CGRP)受体的假定拮抗剂CGRP(8 - 37)所阻断。AM还可减弱缓激肽(BK)诱导的子宫周期性收缩,该作用被AM(22 - 52)或CGRP(8 - 37)所阻断,而AM对催产素或前列腺素F2α(PGF2α)引起的周期性收缩无影响。逆转录-聚合酶链反应(RT-PCR)分析表明,大鼠子宫中表达降钙素受体样受体(CRLR)、受体活性修饰蛋白(RAMP)1、RAMP2和RAMP3的信使核糖核酸(mRNA)。这些结果表明,AM通过激活AM和CGRP的受体选择性抑制自发性和BK诱导的周期性收缩。