CGRP CONTROL OF HUMAN MYOMETRIAL CONTRACTILITY

University Of Texas Medical Br Galveston, Galveston TX

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Abstract

Uterine quiescence is a requirement for me successful completion of term gestation. Failure to maintain uterine relaxation often results in preterm delivery- one of the leading causes of infant mortality and morbidity. Calcitonin gene-related peptide (CGRP) has been demonstrated to be involved in the regulation of blood pressure and myocardial contractility via its potent smooth muscle relaxant property, but its action as a mediator in physiologic and pathologic conditions in uterus is poorly understood. We have obtained new evidence that CGRP relaxes uterine smooth muscle in the rat during pregnancy, but not during labor; CGRP receptors in the rat uterus were modulated by steroid hormones. Further, CGRP relaxes both spontaneous and oxytocin-induced contractile activity in human myometrium, indicating endogenous CGRP may play a role in maintaining human myometrium in a quiescent state during pregnancy. The specific aims of this study are: 1) to examine if myometrial relaxation responses to CGRP are differentially regulated in human during pregnancy and labor, and in nonpregnant state; 2) to ascertain whether receptors for CORP are present in the human myometrium; 3) to determine if these receptors are hormonally regulated; and 4) to investigate postreceptor mechanisms of CORP-relaxing actions. This study will define the role of CORP in the maintenance of human uterine quiescence during pregnancy. Knowledge gained from these studies may assist in designing appropriate therapeutic strategies to reduce premature parturition.