Effects of alpha 2-adrenergic receptor agonist and antagonist drugs on cholinergic contraction in bovine tracheal smooth muscle in vitro

Abstract

Effects of alpha 2-adrenergic receptor stimulation on the cholinergic contractile response of bovine tracheal smooth muscle were studied. To determine the presence and function of alpha2-adrenergic receptors on cholinergic nerves innervating bovine tracheal muscle, effects of 2 alpha 2-adrenoceptor agonists and an antagonist were determined. Muscular contractions were elicited by either electrical field stimulation (EFS) or exogenous acetylcholine (ACH). The contractile response to EFS and exogenous ACH was examined for each tissue. Electrical field stimulation of bovine tracheal smooth muscle caused contractions that were completely abolished by atropine, indicating that predominant excitatory innervation of bovine trachea is cholinergic. The alpha 2 adrenoreceptor agonists clonidine and medetomidine (10(-6) M to 10 (-4) M) concentration-dependently inhibited the contractile response to EFS but not the response to exogenous ACH. Contractions induced by EFS were significantly (P < 0.05) inhibited in clonidine (10(-4) M) - treated tissues at low frequencies (0.01 to 10 Hz), whereas medetomidine (10(-5) M, 10(-4) M) inhibitory effects of the alpha 2-adrenoreceptor agonists clonidine and medetomidine were attenuated by the a2-adrenoreceptor antagonist tolazoline. The alpha 2-agonists used in this study appear to cause prejunctional inhibition of cholinergic nerves, because the smooth muscle contractions elicited by EFS, but not exogenous ACH, were inhibited, compared with controls.