Endothelin-1 (ET)-induced mobilization of intracellular Ca2+ stores from the smooth muscle facilitates sympathetic cotransmission by potentiation of adenosine 5'-triphosphate (ATP) motor activity: studies in the rat vas deferens.
Endothelin-1 (ET) enhances nerve-stimulated contractions in epididymal (E) and prostatic (P) halves of the rat vas deferens, in addition to raising the basal tone in E. Whereas the peak increase in basal tone occurs in about 30 s, the maximal enhancement of neurotransmission is observed within 5 min. The latter effect is long lasting and is maintained even after extensive tissue washout. Furthermore, ET potentiates, in a concentration-dependent fashion, the adenosine 5'-triphosphate (ATP) or the adenylylimidodiphosphate (AMP-PNP) but not the noradrenaline (NA)-induced motor activity. The ATP motor response is partially blocked in media without Ca2+ plus 0.1 mM EGTA or following tissue incubation in buffer containing 10-50 nM nifedipine. However, these procedures do not modify significantly the ET-induced potentiation of the ATP contractions. The ET-induced potentiation of the ATP motor response is not modified by tissue preincubation in Ca(2+)-free buffer plus 10-30 microM ryanodine or 5-20 mM caffeine. The ET-induced rise in E basal tension is significantly reduced in the absence of external Ca2+ or by nifedipine; ryanodine does not modify this effect. Surgical denervation of the tissues does not obliterate the ET-induced potentiation of the ATP motor responses nor the ET increase in E basal tension in tissues superfused in Ca(2+)-free media or buffer with 2.5 mM Ca2+. Endothelin-1 does not significantly modify the overflow of 3H-NA, following transmural electrical depolarization of tissue nerve terminals. Hoe 140 did not interfere with the ET activity.
Donoso
M V
MV
Department of Physiology, Faculty of Biological Sciences, P. Catholic University of Chile, Santiago.
Montes
C G
CG
Lewin
J
J
Fournier
A
A
Calixto
J B
JB
Huidobro-Toro
J P
JP
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D016232:Endothelins; D012433:Ryanodine; D002110:Caffeine; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine