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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 446-453 
    ISSN: 1432-1912
    Keywords: Key words Calcitonin gene-related peptide ; CGRP ; Receptor ; Uterus ; Pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To explore the role of calcitonin gene-related peptide (CGRP) in rat pregnancy, we determined the density of myometrial CGRP-encoded nerve fibre 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 scarce at the parturient stage. In the aorta there was no variation in the density of CGRP fibres with gestation. In nonpregnant rats only, CGRP relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-evoked uterine contractions (EC50 40nM, E max 80%). The effect was antagonized by CGRP[8-37] (pK B 6.47) but was not affected by either blockers of nitric-oxid synthase or ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked by direct depolarization of the cells (TTX-insensitive contractions) (EC50 2nM, E max 70%). In aorta 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 Nω-nitro-l-arginine methyl ester (L-NAME). Amylin neither relaxed the uterus nor the aorta. In pregnant rats, the relaxant effect of CGRP on the uterus was limited on day 21 and was totally absent on day 22 of gestation. We conclude that the primary relaxant effect of CGRP on the uterus occurs at the level of myometrial smooth muscle cells. In the myometrium, gestation decreases CGRP innervation and impairs the relaxant responses to CGRP. Such changes are not observed in vascular tissues like aorta.
    Type of Medium: Electronic Resource
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