EFFECT OF LOCAL ANESTHETICS ON PHARMACOLOGIC RECEPTOR SYSTEMS OF SMOOTH MUSCLE

¹ Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland
² Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of Health, Betesda, Maryland

The effects of tetracaine and lidocaine on contractile responses of rat aorta to norepinephrine and KCl were measured and compared to the antagonism of norepinephrine and KCl by N-(2-chloroethyl)dibenzylamine hydrochloride (Dibenamine). Also, the effect of tetracaine on enrbamylcholine-induced contractions of rat trachea was investigated. Analysis of cumulative dose-response curves showed that the local anesthetics antagonized norepinephrine. carbamylcholine and KCl in a manner similar to that seen with Dibenamine. The initial parallel shift to the right of the norepinephrine and carbamycholine dose-response curves produced by the local anesthetics appeared to be caused by a change in the affinity constant of both the adrenergic and cholinergic receptors. The nonparallel shift in the dose-response curves seen with higher concentrations of the local anesthetics and the noncompetitive antagonism of the response to potassium were probably caused by the well-known effects of local anesthetics on the mobilization of Ca⁺⁺ needed for smooth muscle contraction.