Article date: February 1998
By: C E. Wright, W P. Bowen, T J. Grattan, A H. Morice, in Volume 123, Issue 3, pages 481-486
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 [3H]‐L‐menthol in whole cell membranes prepared from guinea‐pig lung tissue.
In kinetic studies, [3H]‐L‐menthol was found to bind rapidly and reversibly. Binding of [3H]‐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 (t1/2=8 min). [3H]‐L‐menthol was fully dissociated from its binding site within 8 min, (t1/2=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 [3H]‐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.
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 [3H]‐L‐menthol in whole cell membranes prepared from guinea‐pig lung tissue.
In kinetic studies, [3H]‐L‐menthol was found to bind rapidly and reversibly. Binding of [3H]‐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 (t1/2=8 min). [3H]‐L‐menthol was fully dissociated from its binding site within 8 min, (t1/2=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 [3H]‐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
DOI: 10.1038/sj.bjp.0701642
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