Dihydropyridine receptor regulation of acetylcholinesterase biosynthesis.
The dihydropyridine calcium channel antagonist nifedipine causes marked reductions in the amounts of acetylcholinesterase (AchE) molecular forms in primary tissue cultures of avian pectoral muscle. These reductions are time-dependent, requiring passage of 3 h prior to any observable response, dose-dependent, with principal actions occurring in the 1-100 nM range, are greater on the 7 S and 19 S forms than on the 11.4 S form, and, based on susceptibility of AchE to irreversible inhibition by a cationic inhibitor, occur almost exclusively with intracellular AchE coincident with a 2-fold reduction in the rate of secretion. The effects are markedly more pronounced in skeletal muscle than in neurons and differ from those observed for verapamil, diltiazem, and the calcium ionophore A23187. These reductions are incompatible with accelerated protein degradation, alterations in posttranslational processing and assembly in the Golgi complex, or enhanced loss of enzyme to the medium, but instead indicate that nifedipine causes a reduction in AchE biosynthesis. Since AchE forms are thought to arise from a single gene, these findings imply a linkage in skeletal muscle between transcription and posttranscriptional processing of mRNA and ligand occupation of the dihydropyridine receptor.
Decker
M M
MM
Department of Biochemical Pharmacology, State University of New York, Buffalo 14260.
Berman
H A
HA
D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D007527:Isoenzymes / Q000096:biosynthesis*; D009132:Muscles / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology*
D015220:Calcium Channels; D007527:Isoenzymes; D011978:Receptors, Nicotinic; D000001:Calcimycin; D014700:Verapamil; D009543:Nifedipine; D000109:Acetylcholine