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Alteration of the physicochemical properties of triphosphoinositide by nicotinic ligands.

The concentrations of nicotinic drugs required to effect a 50% transfer of triphosphol[3H]isositide from an aqueous phase to a nonaqueous phase closely approximated their concentrations for both in vivo neuromuscular blocking activity and binding to purified nicotinic receptors, and correlated well (correlation coefficient = 0.95)) with their biological activities measured by other workers in an Electrophorus electroplax preparation. The triphospho[3H]inositide transfer induced by nicotinic ligands was dependent on the lipid concentration and was potentiated by Ca2+. The affinity constants of 45Ca2+ for triphosphoinositide were similar to those for the purified nicotinic receptor. These and other findings suggest the possibility that triphosphoinositide (phosphatidylinositol bisphosphate) is a binding site of the nicotinic receptor.