Correlation of ethanol's membrane actions and inhibition of receptor-stimulated histamine release from rat mast cells.
The effects of ethanol and related short-chain alcohols on histamine release from purified rat mast cells were compared to the effects of the alcohols on mast cell membrane properties. Concanavalin A (Con A) (9.3-2790 nM) and somatostatin (0.61-61 microM) stimulated histamine release in a concentration-dependent manner. Ethanol (10-500 mM) had little effect on histamine release itself. However, it inhibited Con A- and somatostatin-stimulated release. Con A was more sensitive to the inhibitory effects of ethanol. For example, 100 mM ethanol inhibited Con A-stimulated release by 56%, whereas somatostatin-stimulated release was reduced only 28%. Mast cell membranes were prepared and the membrane order estimated by determining the fluorescence polarization of diphenylhexatriene. Ethanol (10-500 mM) decreased the fluorescence polarization of mast cell membranes, suggesting a decrease in membrane order. The changes in membrane order by ethanol correlated (r2 = 0.99) with both the inhibition of Con A- and somatostatin-stimulated release. Changes in membrane polarization due to a temperature change from 35 degrees C to 40 degrees C also correlated with changes in receptor-stimulated histamine release. The effects of a series of alcohols related to ethanol on stimulated histamine release and mast cell membrane organization were similar to ethanol and dependent on the lipophilicity of the alcohol. These findings suggest that alcohol effects on membranes can alter receptor function and that certain receptors, e.g., Con A, are more sensitive to the membrane actions of ethanol or related alcohols than are other receptors, e.g., somatostatin.
D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005454:Fluorescence Polarization; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013004:Somatostatin / Q000494:pharmacology; D013696:Temperature
D000438:Alcohols; D003208:Concanavalin A; D000431:Ethanol; D013004:Somatostatin