ALPHA-ADRENOCEPTOR MODULATION OF THE EFFERENT FUNCTION OF CAPSAICIN-SENSITIVE SENSORY NEURONS IN GUINEA-PIG ISOLATED ATRIA

1 Transmural nerve stimulation of guinea-pig atria, obtained from anim als pretreated with reserpine (5 mg kg-1, i.p.), in the presence of at ropine 1-mu-M and of the beta-adrenoceptor blocker CGP 20712A 1-mu-M, induced a positive inotropic effect which was reduced by the calcitoni n gene-related peptide (CGRP) antagonist hCGRP-(8-37) and abolished by pretreatment with capsaicin 1-mu-M. 2 Noradrenaline concentration-dep endently (0.01 - 10-mu-M) reduced the increase in cardiac contractilit y induced by transmural nerve stimulation. The inhibitory effect of no radrenaline was antagonized by yohimbine (0.5 - 1-mu-M), in a dose-dep endent manner. Prazosin (0.5 - 1-mu-M) antagonized the effect of norad renaline and this effect was independent of concentration. 3 In the pr esence of yohimbine, the lower part of the inhibitory-response curve f or noradrenaline was slightly but significantly shifted by prazosin. A similar degree of antagonism was observed in the presence of 1-mu-M p henoxybenzamine. 4 The selective alpha(2) agonists BHT 920 and clonidi ne reduced, in the same concentration-range (0.01 - 1-mu-M), the cardi ac response to transmural nerve stimulation in a yohimbine-sensitive f ashion. 5 Phenylephrine (0.1 - 100-mu-M) and methoxamine (1 - 300-mu-M ) also induced an inhibitory effect on transmural nerve stimulation. T he effect of phenylephrine was antagonized by yohimbine (1-mu-M) more efficiently than by prazosin (0.5-mu-M). 6 These results are in keepin g with the presence of inhibitory prejunctional alpha(2)-adrenoceptors on cardiac sensory nerve endings which modulate the efferent function of capsaicin-sensitive neurones.