title: Studies of the action of nicotine in guinea-pig tracheal smooth muscle: interaction with beta-adrenoceptor antagonists.
abstract: Nicotine produced cholinergic excitatory and adrenergic and non-adrenergic inhibitory responses in isolated guinea-pig trachea. Responses were blocked by hexamethonium (10 micro M), lidocaine (85 micro M) or tetrodotoxin (0.01 micro M) demonstrating that nicotinic receptors in nervous tissue were being activated. In the presence of atropine (0.1 micro M), inhibitory responses to nicotine were partially blocked by specific, experimentally determined, beta-blocking concentrations of pindolol or sotalol or by pretreatment with 6-hydroxydopamine or reserpine but were completely blocked by the less specific beta-blocking drugs 1- and dl-propranolol. Parallel experiments on guinea pig ileum revealed a marked attenuation by dl-propranolol of the atropine sensitive, cholinergic excitatory response to applied nicotine. The non-beta-adrenoceptor blocking agent d-propranolol, produced qualitatively similar attenuation of all excitatory and inhibitory responses to nicotine on both preparations. The remarkable susceptibility of nicotine-induced, neurally mediated responses to low, beta-blocking concentrations of dl-propranolol and to low concentrations of both of its racemates suggests that the non-specific actions of these compounds may have much more significance than is customarily believed. Such studies on the interaction between nicotine and some beta-adrenoceptor blocking drugs are consistent with the hypothesis that non-beta-blocking so-called 'non-specific membrane depressant actions' of dl-propranolol may in concentrations previously considered 'sub-local anaesthetic', significantly depress physiological transmission induced by activation of nicotinic receptors.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D009538:Nicotine