Postjunctional inhibition of contractor responses in the mouse vas deferens by rat and human calcitonin gene‐related peptides (CGRP)

Abstract

3 The inhibitory effect of human ax-CGRP was not antagonized by either propranolol (300 nM) or idazoxan (300 nM), although in the same tissues these latter two drugs reduced responses to isoprenaline and clonidine respectively.4 Rat a-CGRP (100 nM) and human x-CGRP(1.0 yM) did not alter the uptake of[3H]-noradrenaline (30 nM) into mice isolated vasa deferentia. Rat a-CGRP (3-100 nM) did not alter the fractional release per pulse (1.0 Hz, 100 pulses) of tritium from vasa preloaded with [3H]-noradrenaline, although at the same time the peptide inhibited responses of the smooth muscle to field stimulation. 5 Rat and human a-CGRP were equipotent at inhibiting contractions of the mouse vas deferens evoked by acetylcholine although the peptides were less potent than against twitch responses. 6 In the rabbit vas deferens neither rat nor human a-CGRP (3 nM-I A1M) inhibited either twitch responses or acetylcholine contractions. 7 These results suggest that rat and human a-CGRP inhibit contractor responses of the mouse vas deferens not by interference with adrenergic mechanisms, but through postjunctional (possibly CGRP) receptors. A similar mechanism may underlie effects of CGRP in other tissues. The rabbit vas deferens appears to lack the CGRP 'receptors'.

Calcitonin Gene‐related Peptide and Calcitonin in Medullary Thyroid Carcinoma

“…In accordance with these findings immunohistochemical investigations have documented the presence of CGRP in normal as well as neoplastic thyroid C-cells (Williams et al, 1986). Another gene encoding fl-CGRP has recently been described, and shown to be transcribed in MTC (Steenbergh et al, 1985).…”

“…CGRP has been localized in discrete regions of the central nervous system, and at nerve endings adjacent to blood vessels (Rosenfeld et al, 1984). Recent work shows it to be neuropeptide, with profound effects on the cardiovascular system (Brain et al, 1985, Marshall et al, 1986.…”

A Possible Role for Calcitonin-Gene-Related Peptide in the Regulation of the Smooth Muscle Tone of the Bladder and Penis

“…As with the smooth muscle of the vas deferens, in the bladder a postjunctional inhibitory effect of CGRP on excitation and contraction may be assumed. 10 ' 22 Replacement of the CGRP-enriched bladder contents by saline was followed by another brief increase in bladder contraction to stimulation.…”

“…CGRP immunoreactivity has been found extensively throughout the central 1 " 3 and peripheral nervous system. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] CGRP influences a variety of autonomic effects such as vascular tone, 4 " 7 smooth muscle contraction 8 and relaxation, 9 15 and striated muscle relaxation. 16 Additionally, recent findings of CGRP-I in sensory ganglia and nerve fibers, as well as in the adrenal medulla and pituitary gland, 17,18 suggest that CGRP may have sensory and endocrine functions.…”

Structure and autonomic innervation of the human vas deferens: A review

“…While the majority of the intramuscular noradrenergic nerves contained NPY without any of the other neuropeptides tested for, minor populations of TH-IR nerves were identified that contained GAL, CGRP, m-ENK, SOM, or VIP coexistent with NPY. Galanin has been shown previously to be present in the human genitourinary tract where it may play a role in the regulation of smooth muscle tone and motility (Bauer et al, 1986), while CGRP has been reported to have a dosedependent postjunctional inhibitory effect on both excitation and contraction in the mouse vas deferens, mediated predominantly by activation of postganglionic noradrenergic nerve fibres (Al-Kazwini et al, 1986;Ohhanishi and Jacobowitz, 1985). All the m-ENK immunoreactivity observed by Jen et al (1997) was coexistent with TH, and is thus confined to noradrenergic nerves.…”