Straight‐chain alcohols exhibit a cutoff in potency for the inhibition of recombinant glutamate receptor subunits

British Journal of Pharmacology - Tập 133 Số 5 - Trang 651-658 - 2001
B. Emmanuel Akinshola1
1Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA

Tóm tắt

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 IC50 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, IC50 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 IC50: 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.

British Journal of Pharmacology (2001) 133, 651–658; doi:10.1038/sj.bjp.0704112

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British Journal of Pharmacology

Tập 133 Số 5

651-658

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