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'.
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