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 vesamicol-like drugs. The essentially irreversible vesamicol analog inhibits the release of newly synthesized [3H]acetylcholine from stimulated hippocampal slices. Prior activation of protein kinase C with a phorbol ester prevented the inhibition of [3H]acetylcholine release, but activation of protein kinase C after the exposure to the irreversible analog did not prevent the effect of the drug. Binding of 4-aminobenzovesamicol in hippocampal synaptosomes, assayed using [3H]vesamicol and back-titration, was decreased by activation of protein kinase C prior to analog exposure but not by activation subsequent to exposure. We propose that phosphorylation of the vesicular acetylcholine transporter prevents the binding of vesamicol-like drugs.
Clarizia
A D
AD
Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Gomez
M V
MV
Romano-Silva
M A
MA
Parsons
S M
SM
Prado
V F
VF
Prado
M A
MA
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D026901:Membrane Transport Proteins; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
C104300:4-aminobenzovesamicol; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D010880:Piperidines; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D011493:Protein Kinase C; D000109:Acetylcholine