Effect of tetraalkylammonium derivative of 6-methyluracil on amplitude and temporal parameters of miniature endplate potentials in frog neuromuscular junction.
The effect of C-547, a tetraalkylammonium derivative of 6-methyluracil, a novel highly selective acetylcholinesterase inhibitor, on frog neuromuscular junction was studied. In concentrations 10(-9)-10(-7)M the preparation increased the amplitude and temporal parameters of miniature endplate potentials. In contrast to the effect of C-574 on purified acetylcholinesterase from mammals, the effect of this agent on frog neuromuscular junction was reversible. In a concentration of 10(-6)M the preparation apart from anticholinesterase activity produced a parasympatholytic effect manifested in a decrease in amplitude and decay time constant of miniature endplate potentials accompanied by a decrease in spontaneous transmitter secretion. After washout, the parasympatholytic effect recovered more slowly, but disappeared more rapidly compared to anticholinesterase activity. These findings suggest that parasympatholytic effect of C-547 results from direct action on receptor-channel complexes in the endplate membrane.
Gorshkova
O V
OV
Institute of Biochemistry and Biophysics, Russian Academy of Sciences.
Zobov
V V
VV
Bukharaeva
E A
EA
Nikol'skii
E E
EE
Akamsin
V D
VD
Galyametdinova
I V
IV
Reznik
V S
VS
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008564:Membrane Potentials; D009469:Neuromuscular Junction / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011898:Ranidae; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*
C449662:C-547 compound; D004791:Enzyme Inhibitors; D010455:Peptides; D000644:Quaternary Ammonium Compounds; D014498:Uracil; C008378:6-methyluracil; D000110:Acetylcholinesterase; C449663:thymodepressin