The hypothesis is made that some of the wide range of pharmacological effects of tetrahydroisoquinoline metabolites of ethanol (TIQs) may be mediated via effects on the ubiquitous Ca-dependent regulator protein Calmodulin. Calmodulin will be isolated using a new method designed to minize artifactual changes, and effects of TIQs studied on 45Ca binding and 3H-phenothiazine binding sites of pure, soluble Calmodulin. Effects of TIQs will also be studied on membrane-bound Calmodulin, using synaptic plasma membranes (SPM). 45Ca binding, Ca ATPase and opiate receptor radioligand binding activities of SPM will be studied for sensitivity to TIQs, before and after extraction of Calmodulin from SPM. These experiments should provide additional evidence for the role of TIQs in mediating some of the effects of alcohol, and may identify a molecular site of action for TIQs.