Straight-chain alcohols exhibit a cutoff in potency for the inhibition of recombinant glutamate receptor subunits.
The effects of n-alcohols (methanol to 1-decanol) on kainate-activated AMPA receptor subunit GluR1 and GluR3 ion currents were studied in Xenopus oocytes using the two-electrode voltage-clamp recording technique. For short-chain alcohols from methanol to 1-hexanol, potency for inhibition of GluR1 and GluR3 receptor-mediated current increased in proportion to the chain length or hydrophobicity of the alcohol. The IC(50) values of these alcohols for GluR1 were: methanol, 702 mM; ethanol, 170 mM; 1-propanol, 69 mM; 1-butanol, 20 mM; 1-pentanol, 17 mM; and 1-hexanol, 10 mM. For GluR3, IC(50) values were: methanol, 712 mM; ethanol, 238 mM; 1-propanol, 50 mM; 1-butanol, 32 mM; 1-pentanol, 13 mM; and 1-hexanol, 7 mM. For long-chain alcohols, 1-heptanol was less potent than 1-hexanol (estimated IC(50): 19 mM for GluR1 and 18 mM for GluR3), 1-octanol had little effect only on GluR3, and 1-nonanol and 1-decanol did not significantly inhibit both GluR1 and GluR3 responses. The observations indicate that straight-chain n-alcohols exhibit a cutoff in their potency for inhibition of the function of non-NMDA glutamate receptor subunits, GluR1 and GluR3. The cutoff in potency of n-alcohols for inhibition of non-NMDA glutamate receptor function is consistent with the interpretation that alcohols affect the function of these receptor-channels by interacting with an alcohol binding site of specific dimensions on the receptor protein.
Akinshola
B E
BE
Department of Pharmacology, Howard University College of Medicine, Washington DC 20059, USA. eakinshola.edu
D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes; D021122:Protein Subunits; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000187:drug effects; D014982:Xenopus laevis
D000438:Alcohols; D021122:Protein Subunits; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; C104723:glutamate receptor ionotropic, AMPA 3