BETA(2)-ADRENOCEPTORS BUT NOT BETA(3)-ADRENOCEPTORS MEDIATE PREJUNCTIONAL INHIBITION OF NONADRENERGIC NONCHOLINERGIC CONTRACTION OF GUINEA-PIG MAIN BRONCHI

We studied the effects of selective beta-adrenoceptor agonists on the cholinergic and non-adrenergic non-cholinergic (excitatory NANC) contr actions elicited by electrical field stimulation of guinea pig main br onchi in vitro. Addition of the selective beta(2)-adrenoceptor agonist s, fenoterol and salbutamol, and the selective beta(3)-adrenoceptor ag onist, BRL 37344 (3-chlor-phenyl)ethyl)amino]-propyl]-phenoxyacetic ac id), induced a dose-dependent inhibition of the cholinergic contractio n (pD(2) 7.89, 6.71 and 4.56, respectively) and the excitatory NANC re sponse (pD(2) 9.11, 8.16 and 7.42, respectively). Fenoterol- and BRL 3 7344-induced inhibition of the excitatory NANC response was blocked wi th high potency (pK(B) 8.77 and 9.07, respectively) by the selective b eta(2)-adrenoceptor antagonist, ICI 118,511 thylindan-4-yloxy)-3-(isop ropylamino)-butan-2-ol). A comparable contraction induced by neurokini n A (2 or 5 nM) was also inhibited by fenoterol, salbutamol and BRL 37 344, but at significantly higher concentrations than for the inhibitio n of the excitatory NANC response (pD(2) 8.72, 7.56 and 6.66, respecti vely). Such a preferential inhibition of electrical field stimulation- versus agonist-induced effects was not observed for cholinergic contr actions (pD(2) versus methacholine-induced tone 7.86, 6.93 and 5.10, r espectively). The results clearly exclude the involvement of beta(3)-a drenoceptors in these responses. Furthermore they show that beta(2)-ad renoceptors are involved in the prejunctional inhibition of excitatory NANC contractions, presumably via modulation of tachykinin release fr om sensory nerves, and solely in the postjunctional inhibition of chol inergic contractions.