Inhibition by ethanol of contractions of rat vas deferens: no evidence for selective blockade of P2X-purinoceptors.
Some ligand-gated ion channels are important sites of action of ethanol. The aim of the study was to find out whether the P2X-purinoceptors mediating contraction of the rat isolated vas deferens also are selectively sensitive to ethanol. Contractions were elicited by ATP (1 mmol/l), alpha, beta-methylene ATP (0.3 mumol/l), noradrenaline (3 mumol/l), high K+ (20 mmol/l) or electrical (neural) stimulation by pairs of pulses 3 s apart. In electrical stimulation experiments, purinergic and adrenergic response components were isolated by prazosin and suramin, respectively. Concentration-effect curves were determined for ethanol and, for comparison, nifedipine. Tritium outflow from tissues preincubated with 3H-noradrenaline was also examined. Ethanol at relatively low concentrations reduced contractions elicited by high K+ (IC30 145 mmol/l), ATP (IC30 211 mmol/l) and alpha, beta-methylene ATP (IC30 215 mmol/l) as well the purinergic component of neurogenic twitches (IC30 110-126 mmol/l; a significant effect at 10-32 mmol/l) and the adrenergic component of twitch 2 of the twitch pairs (IC30 63 mmol/l). These contractions also were very sensitive to nifedipine. Higher concentrations of ethanol were needed to reduce contractions elicited by noradrenaline (IC30 365 mmol/l) and the adrenergic component of twitch 1 of the twitch pairs (IC30 382 mmol/l), contractions that also were less sensitive to nifedipine. Ethanol 1 mol/l abolished all contractions. In contrast, concentration-effect curves for the inhibition by nifedipine of contractions evoked by ATP, alpha,beta-methylene ATP and noradrenaline (rapid phase) levelled off at 60-70% inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmakologisches Institut, Freiburg, Federal Republic of Germany.
R
R
Bültmann
B
B
Szabo
K
K
Starke
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D015220:Calcium Channels; D011983:Receptors, Purinergic; D000431:Ethanol; D000255:Adenosine Triphosphate; D009543:Nifedipine; D011188:Potassium; D009638:Norepinephrine