Control of the binding of a vesamicol analog to the vesicular acetylcholine transporter

4-AMINOBENZOVESAMICOL was used to test whether activation of protein kinase C protects the vesicular acetylcholine transporter from interaction with v esamicol-like drugs. The essentially irreversible vesamicol analog inhibits the release of newly synthesized [H-3]acetylcholine from stimulated hippoc ampal slices. Prior activation of protein kinase C with a phorbol ester pre vented the inhibition of [3H]acetylcholine release, but activation of prote in kinase C after the exposure to the irreversible analog did not prevent t he effect of the drug. Binding of 4-aminobenzovesamicol in hippocampal syna ptosomes, assayed using [H-3]vesamicol and back-titration, was decreased by activation of protein kinase C prior to analog exposure but not by activat ion subsequent to exposure. We propose that phosphorylation of the vesicula r acetylcholine transporter prevents the binding of vesamicol-like drugs. ( C) 1999 Lippincott Williams & Wilkins.