ENDOTHELIN-INDUCED FACILITATION OF SYMPATHETIC NEUROTRANSMISSION TO THE RAT VAS-DEFERENS - EFFECTS OF SURAMIN

Experiments were conducted to elucidate the mechanisms of action of endothelins in facilitating neurotransmission to the rat isolated vas deferens. Endothelin-1 and endothelin-3 potentiated field stimulation-induced contractions and those evoked by ATP and alpha,beta-methylene ATP. Responses to noradrenaline were unaffected. The C-terminal hexapeptide, endothelin-(16-21) was without effect on neurotransmission. The facilitation by endothelin-l of responses to trains of stimulation (10 Hz for 10 s) was absent in the presence of the P-2-purinoceptor antagonist, suramin, in concentrations which antagonised the contractile effects of alpha,beta-methylene ATP, but not those of noradrenaline. Suramin did not affect 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644)-induced potentiation of contractions in response to field stimulation. These results support the hypothesis that endothelin-induced facilitation of sympathetic neurotransmission to the vas deferens is due to potentiation of the postjunctional effects of the co-transmitter, ATP, acting at P-2X-purinoceptors, and indicate that this effect is mediated through actions at endothelin receptors that are not of the ET(B)-subtype.