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-1 of responses to trains of stimulation (10 Hz for 10 s) was absent in the presence of the P2-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 P2X-purinoceptors, and indicate that this effect is mediated through actions at endothelin receptors that are not of the ETB-subtype.
Lau
W A
WA
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Ventura
S
S
Jiang
Q
Q
Pennefather
J N
JN
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology*; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism; D013498:Suramin / Q000008:administration & dosage / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation
D016232:Endothelins; D006020:Glycopeptides; D011480:Protease Inhibitors; D011983:Receptors, Purinergic; D013498:Suramin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C008890:phosphoramidon; D009638:Norepinephrine