Suppression by metylthioadenosine of histamine or leukotriene-induced contraction in isolated guinea pig tracheal rings: 141

Abstract

Methylthioadenosine(MTA) is a naturally occurring purine nucleoside which has been shown to have numerous effects on cell metabolism and function. We studied the action of MTA on tracheal smooth muscle, using isolated guinea pig tracheal rings. The tracheal rings were suspended in a 10 ml organ bath, containing atropinized Krebs-Henseleit solution. When MTA was added to the medium, relaxation of isolated guinea pig tracheal rings occurred after a latent period and was dose-dependent over concentrations ranging from 50 to 1000 μM. Pretreatment of the tracheal rings with 100 μM MTA inhibited the contraction produced by varying concentrations of histamine or leukotriene D4. The inhibition caused by 100 μM MTA was dependent on histamine or leukotriene D4 concentrations, ie 51% at 0.25 μg/ml histamine, 42.5% at 1.0 μg/ml histamine, 22% at 2.0 μg/ml histamine, and 81% at 0.5 μg LTD4, 50% at 1 μg LTD and 46.2% at 2 μg LTD4. The tracheal contractions induced by a standard concentration of histamine(1 μg/ml or leukotriene D4 (1 μg) were inhibited dose-dependently by pretreatment with MTA, ie 22% (histamine), 8.4%(leukotriene D4 at 10 μM, and 58%(histamine), 25%(leukotriene D4) at 100 μM. 500 μM of MTA blocked completely the contraction induced by histamine or leukotriene D4. It seems that MTA is an important modulator of tracheal smooth muscle cell function.