Differential effect of ketamine on cholinergic- and noncholinergic-induced contractions of isolated guinea-pig bronchi.
Ketamine, 3 X 10(-4) M, was found to inhibit transmural electrical stimulation-induced contractile responses of the mainstem and hilar bronchi isolated from reserpine-pretreated guinea-pigs. This concentration of ketamine did not cause direct smooth muscle relaxation in these preparations and a smaller concentration (3 X 10(-5) M) was ineffective in blocking contractions. The pattern of inhibition produced by ketamine was similar to that produced by atropine, 1 X 10(-6) M, in both preparations and was observed at the larger stimulation frequencies employed. When studied in the presence of atropine to optimize noncholinergic-induced contractions, ketamine did not antagonize contractile responses to transmural electrical stimulation. After pretreatment of the isolated tissues with capsaicin, 1 X 10(-6) M, to optimize cholinergic-induced contractions, ketamine produced inhibition of responses to electrical stimulation. Ketamine, 3 X 10(-4) M, produced a shift to the right of the dose-response curve without altering the maximum contractile responses to carbachol, but had no effect on dose-response curves to substance P, the putative noncholinergic transmitter in these bronchial segments. The data suggest that ketamine exerts a selective inhibitory effect on cholinergically mediated contractions in guinea-pig bronchi and that this antagonism is largely exerted post-junctionally, at the level of the smooth muscle muscarinic receptors.
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D013373:Substance P; D007649:Ketamine; D012110:Reserpine; D002217:Carbachol