Background:Prenatal ethanol exposure is a leading cause of mental retardation. Alcohol damages susceptible neuronal populations through its alteration of signaling pathways that direct cellular activity and survival. In early neural crest cells, ethanol elicits an intracellular Ca²⁺transient that is necessary and sufficient to cause apoptosis. We tested the hypothesis that ethanol's activity represents a saturable and selective effect of alcohols upon this pathway.Methods:Fura‐2–loaded chick embryos, at the 3‐somite stage, were exposed ton‐alcohols ranging in size from ethanol (C2) to decanol (C10). Thereafter, Ca²⁺mobilization was measured using Fura‐2 and ratiometric imaging. Apoptosis was assessed using acridine orange uptake.Results:Ethanol caused the dose‐dependent mobilization of intracellular Ca²⁺within neural crest populations, with an EC₅₀of 52.0 mM.n‐Alcohols displayed increasing potency for Ca²⁺mobilization through pentanol. Hexanol and heptanol were inactive. Unexpectedly, micromolarn‐octanol concentrations triggered significant Ca²⁺release and apoptosis in a G‐protein–dependent manner. Decanol was inactive. Coaddition of either octanol or decanol antagonized the ability of ethanol to stimulate Ca²⁺release.Conclusions:The selective, saturable effect ofn‐alcohols upon Ca²⁺mobilization in neural crest is consistent with a hypothesis that ethanol stimulates these signals through specific interaction with one or more alcohol‐binding sites on a target protein. Octanol may overcome structural constraints imposed upon C6 and C7 in interacting with this protein target; alternatively, it may interact through a unique binding site.

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