IDENTIFICATION OF THE L-MENTHOL BINDING-SITE IN GUINEA-PIG LUNG MEMBRANES

1 L-Menthol inhibits both neurokinin A and capsaicin-induced bronchoco nstriction in the guinea-pig and relaxes pre-constricted guinea-pig is olated bronchi. Structure-activity relationships have been defined for the action of (-)-menthol and related compounds on cold receptors, su ggesting an action of L-menthol at a pharmacological receptor. We have performed radioligand binding studies to characterize the binding sit es for [H-3]-L-menthol in whole cell membranes prepared from guinea-pi g lung tissue. 2 In kinetic studies, [H-3]-L-menthol was found to bind rapidly and reversibly. Binding of [H-3]-L-menthol to lung membranes was found to be time-dependant becoming fully associated to its site w ithin 40 min, and half-maximum association occurred within 8 min (t(1/ 2)=8 min). [H-3]-L-menthol was fully dissociated from its binding site within 8 min, (t(1/2)=2 min). 3 Inhibition studies presented a pharma cological profile of the 'L-menthol site'. Capsaicin, capsazepine, D-m enthol, eugenol, SCH23390 and camphor-were all found to displace [H-3] -L-menthol binding. In contrast WS3, noradrenaline, 5-hydroxytryptamin e, spiperone, flunarazine, bepridil and nicardipine were without effec t. 4 We have identified a L-menthol binding site in the guinea-pig, wh ich may represent a site common to a variety of compounds.