RELAXANT EFFECT OF THE CALCITONIN-GENE-RELATED PEPTIDE (CGRP) ON THE NONPREGNANT AND PREGNANT RAT UTERUS - COMPARISON WITH VASCULAR TISSUE

To explore the role of calcitonin gene-related peptide (CGRP) in rat p regnancy, we determined the density of myometrial CGRP-encoded nerve f ibre terminals and examined, in an organ bath, the relaxant effect of the peptide on uterine strips near parturition. Comparisons were made with the uterus and aorta of nonpregnant rats. In the myometrium, CGRP immunoreactive nerve fibers were abundant in nonpregnant rats and sca rce at the parturient stage. In the aorta there was no variation in th e density of CGRP fibres with gestation. In nonpregnant rats only, CGR P relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-ev oked uterine contractions (EC50 40 nM, E-max 80%). The effect was anta gonized by CGRP[8-37] (pK(B) 6.47) but was not affected by either bloc kers of nitricoxid synthase or ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked by direct depolarization of the cells (TTX-insensitive contractions) (EC50 2 nM, E-max 70%). In a orta contracted with arginine vasopressin, CGRP-induced relaxation was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8-37] (pK(B) 6.90) and was abolished in presence of the nitric oxide synthase inhibitor No-nitro-L-arginine methyl ester (L-NAME). Am ylin neither relaxed the uterus nor the aorta. In pregnant rats, the r elaxant effect of CGRP on the uterus was limited on day 21 and was tot ally absent on day 22 of gestation. We conclude that the primary relax ant effect of CGRP on the uterus occurs at the level of myometrial smo oth muscle cells. In the myometrium, gestation decreases CGRP innervat ion and impairs the relaxant responses to CGRP. Such changes are not o bserved in vascular tissues like aorta.