title: Effects of desipramine on prazosin potency at α1A- and α1D-adrenoceptors in rat vas deferens: implications for the α1L-adrenoceptor subclassification.
abstract: This study investigates the interaction between cocaine, desipramine and prazosin at α1-adrenoceptor subtypes mediating contractions to noradrenaline in epididymal portions of rat vas deferens. Noradrenaline potency was not significantly affected by desipramine (0.1-1.0 μM) and reduced by desipramine (10 μM), but was increased by the presence of cocaine (3.0-30 μM), particularly in terms of phasic contractions to low concentrations of noradrenaline. In vehicle experiments, prazosin exhibited relatively low potency as an antagonist against the predominantly α1A-adrenoceptor mediated response (pKB 8.50). In the presence of cocaine, prazosin exhibited higher potency against the revealed α1D-adrenoceptor mediated component (e.g. pKB 9.12). In the presence of desipramine, the potency of prazosin was either unchanged or indeed decreased. Cocaine (0.3-30 μM) significantly increased the single pulse nerve-stimulation-evoked contraction, with a maximum increase to 156±12% of control (n=9). In contrast, desipramine in low concentrations (0.1-0.3 μM) produced a small but significant increase to 126.6±5.5% (n=11), but higher concentrations failed to increase the response. In conclusion, desipramine fails to produce sufficient noradrenaline transporter block in low concentrations (0.1 μM) and produces α1-adrenoceptor antagonism in slightly higher concentrations (0.3-1 μM), and so is unsuitable for use in α1-adrenoceptor subclassification studies. Contractions of rat vas deferens are mediated by α1A- and α1D-adrenoceptors, and prazosin has selectivity for α1D- over α1A-adrenoceptors. The α1L-adrenoceptor previously identified in rat vas deferens is the native α1A-adrenoceptor. The range of prazosin potencies and receptor subtypes previously reported in rat vas deferens may be explained by the choice of cocaine or desipramine as noradrenaline transporter blocker.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen׳s Green, Dublin 2, Ireland. Electronic address: docherty@rcsi.ie.
authors.forename: J R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin
keywords: Noradrenaline transporter; Prazosin; Rat vas deferens; α1A-adrenoceptor; α1D-adrenoceptor; α1L-adrenoceptor