Prazosin has low potency at α1A-adrenoceptors and high potency at α1D -adrenoceptors in rat vas deferens.
(1) We have investigated α1 -adrenoceptor subtypes mediating contractions to noradrenaline in epididymal portions of rat vas deferens. (2) Contractions to noradrenaline were investigated in the absence or presence of the noradrenaline transporter blocker cocaine. (3) In the absence of cocaine, contractions to noradrenaline were potently antagonized by RS100329, but not by BMY7378, and so are mediated mainly by α1A -adrenoceptors. (4) In the presence of cocaine, noradrenaline potency was increased, particularly in terms of low concentrations and phasic contractions. Contractions to low concentrations of noradrenaline in the presence of cocaine were resistant to RS100329 but potently antagonized by BMY7378, demonstrating that α1D-adrenoceptors are additionally involved in contractions amplified by cocaine. (5) In the absence of cocaine, prazosin exhibited relatively low potency as an antagonist against the α1A-adrenoceptor-mediated component to the response. In the presence of cocaine, prazosin exhibited higher potency against the α1D-adrenoceptor-mediated component. (6) In conclusion, prazosin has previously unreported selectivity for α1D-over α1A -adrenoceptors in functional studies of rat vas deferens. Contractions of rat vas deferens are mediated by α1A-and α1D -adrenoceptors. The range of prazosin potencies and of receptor subtypes previously reported in rat vas deferens may be explained by the presence of these two subtypes.
Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, Ireland.
J R
JR
Docherty
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D013941:Thymine / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology
D018759:Adrenergic Uptake Inhibitors; D058668:Adrenergic alpha-1 Receptor Antagonists; D010879:Piperazines; C120711:RS 100329; D018340:Receptors, Adrenergic, alpha-1; D003042:Cocaine; C053428:BMY 7378; D013941:Thymine; D009638:Norepinephrine; D011224:Prazosin
BMY7378; RS100329; noradrenaline transporter; prazosin; rat vas deferens; α1A-adrenoceptor; α1D-adrenoceptor; α1L-adrenoceptor