Effects of desipramine on prazosin potency at alpha(1A)- and alpha(1D)-adrenoceptors in rat vas deferens: Implications for the alpha(1L)-adrenoceptor subclassification

摘要

This study investigates the interaction between cocaine, desipramine and prazosin at alpha(1)-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 mu M) and reduced by desipramine (10 mu M), but was increased by the presence of cocaine (3.0-30 mu M), 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 (alpha(1A)-adrenoceptor mediated response (pK(B) 8.50). In the presence of cocaine, prazosin exhibited higher potency against the revealed alpha(1D)-adrenoceptor mediated component (e.g. pK(B) 9.12). In the presence of clesipramine, the potency of prazosin was either unchanged or indeed decreased. Cocaine (0.3-30 mu M) 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 mu M) 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 mu M) and produces alpha(1)-adrenoceptor antagonism in slightly higher concentrations (0.3-1 mu M), and so is unsuitable for use in alpha(1)-adrenoceptor subclassification studies. Contractions of rat vas deferens are mediated by alpha(1A)- and alpha(1D)-adrenoceptors, and prazosin has selectivity for ally over alpha(1A)-adrenoceptors. The alpha(1L)-adrenoceptor previously identified in rat vas deferens is the native alpha(1A)-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 blacker. (C) 2014 Elsevier B.V. All rights reserved.