Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids.
Effects of common monoterpenoid alcohols and ketones were investigated on recombinant human gamma-aminobutyric acid A (GABAA; alpha1beta2gamma2s) and glycine (alpha1 homomers) receptors expressed in Xenopus oocytes. GABA currents were enhanced by coapplications of 10-300 microM: (+)-menthol>(-)-menthol>(-)-borneol>>(-)-menthone=camphor enantiomers>carvone enantiomers, with menthol acting stereoselectively. By contrast, thujone diastereomers inhibited GABAA receptor currents while glycine currents were only markedly potentiated by menthol. Positive modulation by (+)-menthol was explored given its pronounced effects (e.g., at 100 microM, GABA and glycine EC20 responses increased by 496+/-113% and 135+/-56%, respectively). (+)-Menthol, 100 microM, reduced EC50 values for GABA and glycine from 82.8+/-9.9 to 25.0+/-1.8 microM, and from 98.7+/-8.6 to 75.7+/-9.4 microM respectively, with negligible effects on maximal currents. This study reveals a novel neuroactive role for menthol as a stereoselective modulator of inhibitory ligand-gated channels.
Hall
Adam C
AC
Neuroscience Program, Department of Biological Sciences, Clark Science Center, Smith College, Northampton, MA 01063, USA. ahall@science.smith.edu
Turcotte
Carolyn M
CM
Betts
Brooke A
BA
Yeung
Wing-Yee
WY
Agyeman
Abena S
AS
Burk
Lâle A
LA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008610:Menthol / Q000737:chemistry / Q000494:pharmacology*; D039821:Monoterpenes / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D018009:Receptors, Glycine / Q000235:genetics / Q000502:physiology*; D013237:Stereoisomerism; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D039821:Monoterpenes; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D008610:Menthol; D005680:gamma-Aminobutyric Acid; D005998:Glycine