Characterization of the prejunctional beta adrenoceptors in canine bronchial smooth muscle

Prejunctional beta adrenoceptors in canine bronchi (3rd to 6th order) were characterized by observing the effects of beta receptor agonists and antagonists on field stimulation-induced contractions and excitatory junction potentials (EJPs). Contractions were antagonized by norepinephrine (IC50 = 9.4 X 10(-7) M), isoproterenol (IC50 = 1.9 X 10(-8) M) or salbutamol (IC50 = 4.0 X 10(-8) M). EJPs were also decreased by all three agonists, with little or no effect on resting membrane potential or on carbachol-induced depolarization when used at concentrations sufficient to eliminate EJPs. These inhibitory effects were blocked by propranolol or timolol, as well as by the selective antagonists ICI 89,406 (beta-1-selective) and ICI 118,551 (beta-2-selective); pA2 values for the selective antagonists were 8.4 and 7.2 (norepinephrine as agonist) or 6.5 and 9.0 (salbutamol as agonist), respectively. Control responses were also sometimes potentiated by the nonselective antagonists. Schild plot analysis of the data indicated clearly that both beta-1 and beta-2 receptors are involved in the inhibitory effect. Electron microscopic studies showed this tissue to be densely innervated by adrenergic and cholinergic nerves with close apposition of adrenergic and cholinergic nerve varicosities, providing a structural basis for prejunctional interactions between them. From the data presented, we conclude that catecholamines act on prejunctional beta-1 and beta-2 receptors leading to inhibition of cholinergic neurotransmission in canine bronchi.