Identification of the L-menthol binding site in guinea-pig lung membranes.
1. 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. 2. 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-dependent 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). 3. 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. 4. We have identified a L-menthol binding site in the guinea-pig, which may represent a site common to a variety of compounds.
Wright
C E
CE
Department of Medicine, Northern General Hospital, Sheffield.
Bowen
W P
WP
Grattan
T J
TJ
Morice
A H
AH
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001665:Binding Sites; D002164:Camphor / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005054:Eugenol / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008610:Menthol / Q000378:metabolism*; D011869:Radioligand Assay; D014316:Tritium
D001552:Benzazepines; D014316:Tritium; D008610:Menthol; D005054:Eugenol; D002164:Camphor; C071423:capsazepine; D002211:Capsaicin