Vol. 298, Issue 2, 623-633, August 2001

₂-Adrenoceptor-Mediated Prejunctional Facilitation and Postjunctional Inhibition of Sympathetic Neuroeffector Transmission in the Guinea Pig Vas Deferens

Latchezar D. Todorov, Rory Clerkin, Svetlana T. Mihaylova-Todorova, Mohammad A. Khoyi and David P. Westfall

Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada

This study examines the role of prejunctional and postjunctional -adrenoceptors in the modulation of sympathetic cotransmission in the guinea pig vas deferens. The prejunctional involvement of -adrenoceptors was evaluated by testing the effects of several agonists and antagonists on the nerve stimulation-evoked overflow of ATP and norepinephrine (NE) from the "in vitro" vas deferens. The nonsubtype-selective -adrenoceptor agonist isoproterenol and the ₂-subtype-selective agonist clenbuterol increased, to a similar degree, the overflow of ATP and NE, while the ₁-subtype-selective agonist xamoterol and the ₃-subtype-selective agonist BRL 37 344 had no effect. Pretreatment with ICI 118, 551, a ₂-subtype-selective antagonist, abolished the facilitation of cotransmitter release by isoproterenol and clenbuterol, while the ₁-subtype-selective antagonist atenolol had no effect. Activation of -adrenoceptors by either isoproterenol or clenbuterol, but not by xamoterol and BRL 37 344, reduced the amplitude of contractions evoked by exogenously applied ATP. Pretreatment with propranolol or ICI 118, 551, but not atenolol, prevented these inhibitory effects. Isoproterenol in lower concentrations produced dose-dependent reduction of the purinergic but not the adrenergic phase of nerve stimulation-induced contraction of the guinea pig vas deferens. When applied in concentrations greater than 1 µM, isoproterenol, but not clenbuterol, actually produced a concentration-dependent facilitation of contractions evoked by both nerve stimulation and exogenously applied ATP. Antagonists of -adrenoceptors blocked these facilitatory effects. Together, these results demonstrate that ₂-adrenoceptors can influence sympathetic neuroeffector transmission both prejunctionally, where they facilitate equally well the release of sympathetic cotransmitters and postjunctionally, where they inhibit smooth muscle contractions evoked by ATP.