Endothelin-1 selectively potentiates the purinergic component of sympathetic neurotransmission in rat seminal vesicle.
Endothelin-1 (ET-1; 3-100 nM) caused graded tonic contractions and enhanced neurogenic contractions in rat field-stimulated seminal vesicle. At 100 nM, ET-1 increased nerve-mediated responses by 350 +/- 74 mg/100 mg wet tissue (almost 100% potentiation), whereas sarafotoxin S6c was ineffective. The potentiation of neurogenic responses by ET-1 was virtually abolished by the ETA receptor antagonist BQ-123 (1 microM; c. 95% inhibition) but was not modified by the ETB receptor antagonist BQ-788 (1 microM). Responses to field stimulation were inhibited by tetrodotoxin (0.1 microM; 100%), guanethidine (GTD; 5 microM, 75%), prazosin (PRA; 0.1 microM, 90%), desensitization of P2x purinoceptors with alpha,beta-methylene-ATP (mATP; 10 microM, 50%), or atropine (ATR; 0.1 microM, 40%). ET-1-induced potentiation of neurogenic contractions was not modified by prior incubation with indomethacin (5.6 microM), ATR, or PRA, but mATP and GTD reduced the effects of 100 nM ET-1 to 189 +/- 76 and 5 +/- 7 mg/100 mg wet tissue, respectively (n = 6-8). Therefore, ET-1 enhances nerve-mediated responses of this tissue by selectively potentiating the purinergic component of sympathetic neurotransmission. This action, which is independent of the eicosanoid-cycloxygenase pathway, is mediated via ETA receptors and, at least in part, by enhancement of motor responses to ATP.
Luciano
L G
LG
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
D'Orléans-Juste
P
P
Calixto
J B
JB
Rae
G A
GA
D000818:Animals; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists; D011983:Receptors, Purinergic / Q000187:drug effects*; D012669:Seminal Vesicles / Q000187:drug effects / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D011983:Receptors, Purinergic; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6