PREJUNCTIONAL ACTIONS OF N-ETHYL-MALEIMIDE AND PHENOXYBENZAMINE IN RAT VAS-DEFERENS

In studies of electrically evoked isometric contractions of rat vas de ferens, N-ethyl-maleimide (30 mu M) pretreatment significantly reduced the prejunctional inhibitory potencies of xylazine and 5-hydroxytrypt amine but failed to affect the potency of the alpha(1)-adrenoceptor ag onist amidephrine. Phenoxybenzamine (1 mu M) or N-ethoxycarbonyl-2-eth oxy-1,2-dihydroquinoline (EEDQ) (10 mu M) produced significant shifts in the potency of xylazine and significantly reduced the maximum inhib ition, but the combination of phenoxybenzamine or EEDQ and N-ethyl-mal eimide (30 mu M) produced no further alteration in the effects of xyla zine. In displacement studies, N-ethyl-maleimide displaced the binding of [H-3]MK 912 -benzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2' one ) to rat renal cortex membranes with a K-i of 466 +/- 133 mu M (n = 5) , and so does not bind to alpha(2)-adrenoceptors in the concentration range in which it affects prejunctional receptor mediated responses. T his may suggest that N-ethyl-maleimide has actions other than inactiva tion of G-proteins or that the irreversible alpha(2)-adrenoceptor anta gonists phenoxybenzamine and EEDQ inactivate G-proteins sensitive to N -ethyl-maleimide in concentrations at which they bind to alpha(2)-adre noceptors.