DIFFERENTIAL SENSITIVITY OF HUMAN NONPREGNANT AND PREGNANT MYOMETRIUMTO CALCITONIN-GENE-RELATED PEPTIDE

OBJECTIVES: Calcitonin gene-related peptide (CGRP) is a smooch muscle relaxant with potent vasodilating properties. To investigate its inhib itory effects on human myometrial contractions, we obtained excised hu man myometria from term pregnant, with and without spontaneous labor, and nonpregnant patients. METHODS: Myometrial strips were mounted in t issue baths in which contractile activity tvas recorded. Spontaneously contracting tissues in vitro were exposed to increasing concentration s of CGRP (10(-11)-10(-7) mol/L). Tissues without spontaneous contract ions were induced to contract with either oxytocin or KCl before being exposed to CGRP. The IC25 (CGRP concentration required to inhibit con tractility by 25%) was used as comparison between groups. RESULTS: Tis sues with spontaneous or oxytocin-induced in vitro contractions respon ded equally to CGRP relaxation. Tissues induced to contract with KCl i n vitro required approximately 2000 times more CGRP for equal relaxati on. In tissues with spontaneous or oxytocin-induced in vitro contracti ons, those from pregnant unlabored patients were 60 times more sensiti ve to CGRP than those from pregnant labored or nonpregnant patients. T he latter two groups responded equally to CGRP. CONCLUSIONS: The sensi tivity of myometrial tissues to CGRP relaxation in vitro is increased from the nonpregnant to the pregnant term state. This increased sensit ivity is lost once patients develop spontaneous term labor. The relati ve ineffectiveness of CGRP in relaxing KCl-induced in vitro contractio ns probably reflects its known mechanism of action, namely the hyperpo larization of cell membrane potentials via activation of membrane pota ssium channels. Copyright (C) 1997 by the Society for Gynecologic Inve stigation.