Differential sensitivity of human nonpregnant and pregnant myometrium to calcitonin gene-related peptide

OBJECTIVES: Calcitonin gene-related peptide (CGRP) is a smooch muscle relaxant with potent vasodilating properties. To investigate its inhibitory effects on human myometrial contractions, we obtained excised human myometria from term pregnant, with and without spontaneous labor, and nonpregnant patients. METHODS: Myometrial strips were mounted in tissue baths in which contractile activity tvas recorded. Spontaneously contracting tissues in vitro were exposed to increasing concentrations of CGRP (10(-11)-10(-7) mol/L). Tissues without spontaneous contractions were induced to contract with either oxytocin or KCl before being exposed to CGRP. The IC25 (CGRP concentration required to inhibit contractility by 25%) was used as comparison between groups. RESULTS: Tissues with spontaneous or oxytocin-induced in vitro contractions responded equally to CGRP relaxation. Tissues induced to contract with KCl in vitro required approximately 2000 times more CGRP for equal relaxation. In tissues with spontaneous or oxytocin-induced in vitro contractions, those from pregnant unlabored patients were 60 times more sensitive to CGRP than those from pregnant labored or nonpregnant patients. The latter two groups responded equally to CGRP. CONCLUSIONS: The sensitivity of myometrial tissues to CGRP relaxation in vitro is increased from the nonpregnant to the pregnant term state. This increased sensitivity is lost once patients develop spontaneous term labor. The relative ineffectiveness of CGRP in relaxing KCl-induced in vitro contractions probably reflects its known mechanism of action, namely the hyperpolarization of cell membrane potentials via activation of membrane potassium channels. Copyright (C) 1997 by the Society for Gynecologic Investigation.