Differential inhibition of soluble and membrane-bound acetylcholinesterase forms from mouse brain by choline esters with an acyl moiety of an intermediate size.
Differential inhibitions of soluble and membrane-bound acetylcholinesterase forms purified from mouse brain were examined by the comparison of kinetic constants such as a Km value, a Kss value (substrate inhibition constant), and IC50 values of active site-selective ligands including choline esters. Membrane-bound acetylcholinesterase form (solubilized only in the presence of detergent) showed lower Km and Kss values than soluble acetylcholinesterase form (easily solubilized without detergent). Edrophonium expressed a slightly but significantly (p < 0.01) higher inhibition of detergent-soluble acetylcholinesterase form than aqueous-soluble acetylcholinesterase form, while physostigmine inhibited both forms with a similar potency. A remarkable difference in inhibition was observed using choline esters; although choline esters with acyl chain of a short size (acetyl- to butyrylcholine) or a long size (heptanoyl- to decanoylcholine) showed a similar inhibitory potency for two forms of acetylcholinesterase, pentanoylcholine and hexanoylcholine inhibited more strongly aqueous-soluble acetylcholinesterase than detergent-soluble acetylcholinesterase. Thus, it is suggested that the two forms of AChE may be distinguished kinetically by pentanoyl- or hexanoylcholine.
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Advanced Technology Research Center, Agency for Defense Development, Yuseong, Taejon, Korea.
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D000166:Acridines; D000215:Acylation; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002794:Choline / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002846:Chromatography, Affinity; D004952:Esters; D007700:Kinetics; D008566:Membranes / Q000201:enzymology; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D012995:Solubility
D000166:Acridines; D002800:Cholinesterase Inhibitors; D004952:Esters; C028189:N-methylacridine; D002794:Choline