β2- but not β3-adrenoceptors mediate prejunctional inhibition of non-adrenergic non-cholinergic 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) contractions elicited by electrical field stimulation of guinea pig main bronchi in vitro. Addition of the selective beta(2)-adrenoceptor agonists, fenoterol and salbutamol, and the selective beta(3)-adrenoceptor agonist, BRL 37344 (4-[2-[(2-hydroxy-2(3-chlor-phenyl)ethyl)amino]-propyl]-phenoxyacetic acid), induced a dose-dependent inhibition of the cholinergic contraction (pD(2) 7.89, 6.71 and 4.56, respectively) and the excitatory NANC response (pD(2) 9.11, 8.16 and 7.42, respectively). Fenoterol- and BRL 37344-induced inhibition of the excitatory NANC response was blocked with high potency (pK(B) 8.77 and 9.07, respectively) by the selective beta(2)-adrenoceptor antagonist, ICI 118,511 (erythro-1-(7-methylindan-4-yloxy)-3-(isopropylamino)-butan-2-ol). A comparable contraction induced by neurokinin A (2 or 5 nM) was also inhibited by fenoterol, salbutamol and BRL 37344, but at significantly higher concentrations than for the inhibition of the excitatory NANC response (pD(2) 8.72, 7.56 and 6.66, respectively). Such a preferential inhibition of electrical field stimulation- versus agonist-induced effects was not observed for cholinergic contractions (pD(2) versus methacholine-induced tone 7.86, 6.93 and 5.10, respectively). The results clearly exclude the involvement of beta(3)-adrenoceptors in these responses. Furthermore they show that beta(2)-adrenoceptors are involved in the prejunctional inhibition of excitatory NANC contractions, presumably via modulation of tachykinin release from sensory nerves, and solely in the postjunctional inhibition of cholinergic contractions.