Identification of the L ‐menthol binding site in guinea‐pig lung membranes

L ‐Menthol inhibits both neurokinin A and capsaicin‐induced bronchoconstriction in the guinea‐pig and relaxes pre‐constricted guinea‐pig isolated bronchi. Structure‐activity relationships have been defined for the action of (−)‐menthol and related compounds on cold receptors, suggesting an action of L ‐menthol at a pharmacological receptor. We have performed radioligand binding studies to characterize the binding sites for [ 3 H]‐ L ‐menthol in whole cell membranes prepared from guinea‐pig lung tissue. In kinetic studies, [ 3 H]‐ L ‐menthol was found to bind rapidly and reversibly. Binding of [ 3 H]‐ L ‐menthol to lung membranes was found to be time‐dependant becoming fully associated to its site within 40 min, and half‐maximum association occurred within 8 min ( t 1/2 =8 min). [ 3 H]‐ L ‐menthol was fully dissociated from its binding site within 8 min, ( t 1/2 =2 min). Inhibition studies presented a pharmacological profile of the ‘ L ‐menthol site’. Capsaicin, capsazepine, D ‐menthol, eugenol, SCH23390 and camphor were all found to displace [ 3 H]‐ L ‐menthol binding. In contrast WS3, noradrenaline, 5‐hydroxytryptamine, spiperone, flunarazine, bepridil and nicardipine were without effect. We have identified a L ‐menthol binding site in the guinea‐pig, which may represent a site common to a variety of compounds.British Journal of Pharmacology (1998) 123 , 481–486; doi: 10.1038/sj.bjp.0701642