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Relaxant effect of amiloride on canine tracheal smooth muscle

IK Krampetz and R Bose

Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.

Amiloride, a K+-sparing diuretic, relaxed canine tracheal smooth muscle strips contracted isometrically with high potassium (KCl), carbachol, serotonin and histamine. This indicated that relaxation was not linked to an interaction with an agonist specific receptor. Amiloride-induced relaxation was also not mediated through the production of relaxant prostaglandins, or by the endogenous release of catecholamines. During potassium contractions, amiloride addition produced a slow monophasic, dose-dependent relaxation (IC50 = 12.3 microM). In carbachol contracted strips, 1 and 10 microM amiloride induced a slow monophasic relaxation. With 35 to 250 microM, an initial rapid phase (IC50 = 75.5 microM) was superimposed onto this slow phase (IC50 = 23.5 microM), producing a biphasic relaxation. The rates of relaxation decreased with increased external [Na+] regardless of stimulus, suggesting possible competitive inhibition of a sodium-dependent process. Exposure caused a rapid decline in tension followed by a recovery phase. Tension maintenance during potassium contraction decreased transiently upon the addition of acid to a much lesser extent. Amiloride (100 microM) depressed tension recovery after acid exposure in both cases. Based on the known actions of this drug, inhibition of the Na+-H+ antiporter appears to be consistent with these data. This suggests amiloride may well belong to a new class of smooth muscle relaxants.

Volume 246, Issue 2, pp. 641-648, 08/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. J. Christ, L. M. Iwamoto, A. d. Silva, S. L. Lavallee, and K. T. Nakamura
Amiloride-induced contraction of isolated guinea pig, mouse, and human fetal airways
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1998; 274(1): R209 - R213.
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