Adrenomedullin inhibits spontaneous and bradykinin-induced but not oxytocin- or prostaglandin F(2α)-induced periodic contraction of rat uterus

Abstract

In isolated rat uterine strips, adrenomedullin (AM) inhibited the spontaneous periodic contraction in a concentration-dependent manner (IC50 = 22.3 ± 0.7 nM). The inhibitory effect of AM was prevented by either AM22-52, 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 AM22-52 or CGRP8-37, whereas AM had no effect on the periodic contraction caused by oxytocin or prostaglandin F(2α) (PGF(2α). 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.