beta(2)-adrenoceptor-mediated prejunctional facilitation and postjunctional inhibition of sympathetic neuroeffector transmission in the guinea pig vas deferens

This study examines the role of prejunctional and postjunctional beta -adre noceptors in the modulation of sympathetic cotransmission in the guinea pig vas deferens. The prejunctional involvement of beta -adrenoceptors was eva luated by testing the effects of several agonists and antagonists on the ne rve stimulation-evoked overflow of ATP and norepinephrine (NE) from the "in vitro" vas deferens. The nonsubtype-selective beta -adrenoceptor agonist i soproterenol and the beta (2)-subtype-selective agonist clenbuterol increas ed, to a similar degree, the overflow of ATP and NE, while the beta (1)-sub type-selective agonist xamoterol and the beta (3)-subtype-selective agonist BRL 37 344 had no effect. Pretreatment with ICI 118, 551, a beta (2)-subty pe-selective antagonist, abolished the facilitation of cotransmitter releas e by isoproterenol and clenbuterol, while the beta (1)-subtype-selective an tagonist atenolol had no effect. Activation of beta -adrenoceptors by eithe r isoproterenol or clenbuterol, but not by xamoterol and BRL 37 344, reduce d the amplitude of contractions evoked by exogenously applied ATP. Pretreat ment with propranolol or ICI 118, 551, but not atenolol, prevented these in hibitory effects. Isoproterenol in lower concentrations produced dose-depen dent reduction of the purinergic but not the adrenergic phase of nerve stim ulation-induced contraction of the guinea pig vas deferens. When applied in concentrations greater than 1 muM, isoproterenol, but not clenbuterol, act ually produced a concentration-dependent facilitation of contractions evoke d by both nerve stimulation and exogenously applied ATP. Antagonists of a-a drenoceptors blocked these facilitatory effects. Together, these results de monstrate that beta (2)-adrenoceptors can influence sympathetic neuroeffect or transmission both prejunctionally, where they facilitate equally well th e release of sympathetic cotransmitters and postjunctionally, where they in hibit smooth muscle contractions evoked by ATP.