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

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Abstract
The effects of rat and human .alpha.-calcitonin gene-related peptide (CGRP) were compared in the mouse and rabbit isolated vas deferens preparation contracted by either field stimulation or acetylcholine. The peptides were about equipotent at inhibiting twitch responses of the mouse vas deferens to field stimulation at 0.2 Hz (IC50 12 .+-. 4 nM and 15 .+-. 3 nM, rat and human .alpha.-CGRP respectively). Rat .alpha.-CGRP was less potent at inhibiting responses to 10 Hz than to either 0.2 Hz or 1.0 Hz stimulation. The potency of rat .alpha.-CGRP at 1.0 Hz was unaltered by halving the calcium concentration of the Krebs solution. The inhibitory effect of human .alpha.-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. Rats .alpha.-CGRP(100 nM) and human .alpha.-CGRP (1.0 .mu.M) did not alter the uptake of [3H]-noradrenaline (30 nM) into mice isolated vasa deferentia. Rat .alpha.-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. Rat and human .alpha.-CRGP were equipotent at inhibiting contractions of the mouse vas deferens evoked by acetylcholine although the peptides were less potent than against twitch responses. In the rabbit vas deferens neither rat nor human .alpha.-CGRP (3 nM-1 .mu.M) inhibited either twitch responses or acetylcholine contractions. These results suggest that rat and human .alpha.-CGRP inhibit contractor responses of the mouse vas deferens not by interferences 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.