Relaxant effect of the calcitonin gene-related peptide (CGRP) on the nonpregnant and pregnant rat uterus. Comparison with vascular tissue

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 40 nM, Emax 80%). The effect was antagonized by CGRP[8-37] (pKB 6.47) but was not affected by either blockers 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, Emax 70%). In aorta contracted with arginine vasopressin, CGRP-induced relaxation was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8-371 (pKB 6.90) and was abolished in presence of the nitric oxide synthase inhibitor Nomega-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.

Innervation and Immunohistochemical Characteristics of Epididymis in Alpaca Camelid (Vicugna Pacos)

“…The NPY-containing nerves are also distributed intimately with the epithelial cells of the monkey ejaculatory duct which have few ultrastructural features indicating a positive secretory activity (Yokoyama, 1989). CGRP was considered a marker of sensory nerves (Yamada et al, 1977;Ngassapa et al, 1998) and had numerous biological functions like relaxing non vascular smooth musculature (Anouar et al, 1998;Yousufzai and Abdel-Latif, 1998;Hislop et al, 1998) and modulating sensory signals (Häppola and Lakomy, 1989;Csillik et al, 1993) and together to SP were involved in the control of the pain sensation (Santicioli et al, 1988). Rare SP-and CGRP-positive nerve fibres were found in alpaca, thus confirming the results in the camel epididymis (Saleh et al, 2002).…”

Mechanisms Involved in Calcitonin Gene-Related Peptide-Induced Relaxation in Pregnant Rat Uterine Artery1

“…3A) inhibited the CGRP-induced vascular relaxation effects in pregnant uterine arteries partially but significantly. Studies of Anouar et al [36] suggested that the relaxant effects of CGRP are abolished by inhibitors of nitric oxide synthase in rat aortas but not in the uterus. Recent studies in mouse uteri demonstrated that the relaxation of the myometrium by CGRP is independent of nitric oxide synthase activity [37].…”

A Functional Genomic Study to Identify Differential Gene Expression in the Preterm and Term Human Myometrium1

“…We observed a noticeable reduction in the expression of the CGRP (calcitonin gene-related peptide)-receptor transcript at term. According to Anouar et al [20] and to Dong et al [21], the loss of CGRP response at term could contribute to initiation of rat and human labor. An up-regulation of a calmodulin-dependent phosphodiesterase (PDE-1) was observed at term as it has been clearly established in human term myometrium [22].…”