Mechanisms of the relaxant action of ketamine on isolated porcine trachealis muscle.

ABSTRACT

Ketamine is a potent bronchodilator, but its mode of action is unclear. We have studied the effect of ketamine on the peripheral vagus nerve motor pathway of isolated porcine trachealis muscle. Postsynaptic nicotinic cholinergic receptors of the intramural ganglia were stimulated selectively with 1,1-dimethyl-4-phenyl-piperazinium iodide, post-ganglionic nerve fibres with electrical field stimulation (in the presence of hexamethonium) and muscarinic cholinergic receptors with acetylcholine (in the presence of tetrodotoxin). Ketamine 10(-4) mol litre-1 significantly shifted the concentration-response curves of acetylcholine (P < 0.02) and electrical field stimulation (P < 0.001) to the right and abolished the response to 1,1-dimethyl-4-phenyl-piperazinium iodide (P < 0.02). Ketamine also caused a concentration-dependent relaxation of muscle strips precontracted with acetylcholine. This was unaffected by propranolol. Ketamine relaxed muscle strips precontracted with potassium chloride, in the absence and presence of atropine. We conclude that ketamine interacts with the peripheral vagus nerve by decreasing the excitability of the postsynaptic nicotinic receptors of the intramural ganglia, and by affecting the muscarinic receptor, smooth muscle, or both. Beta-2 adrenoceptors are not involved in the mechanism of relaxation.