Effect of tetracaine on membrane-bound acetylcholinesterase activity and anilinonaphthalene sulphonate-induced membrane fluorescence.
Tetracaine (25-300 microM) reversibly inhibits (in vitro) AChE activity of rat brain synaptosome (4.4-100%) and erythrocyte membrane (3.9-65.2%) in a concentration dependent manner. IC50 values of tetracaine for AChE of synaptosome and erythrocyte membrane are 88 and 200 microM respectively. At sub-inhibitory concentrations (less than or equal to 10 microM) tetracaine activates (8.7-23%) AChE of synaptosome but not of erythrocyte membrane. Lineweaver-Burk plots indicate that tetracaine-induced inhibition of AChE is competitive in nature and Ki value decreases on increasing the concentration (greater than 100 microM) of tetracaine in both synaptosome and erythrocyte membrane. Tetracaine (25-500 microM) produces a concentration dependent increase in 1-anilino-8-naphthalene sulphonate (ANS)-induced relative fluorescence (F470) of both synaptosomal (6.5-102%) and erythrocyte membrane (2.4-53.3%) without shifting their emission maxima (470 nm). Further it is also noted that the quantum yield of F470 of both the membranes increases with the increase of tetracaine concentrations (100-500 microM). These results suggest that the interaction of tetracaine with both the enzyme and its lipid microenvironment may be the cause of inhibition of membrane-bound AChE activity.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000817:Anilino Naphthalenesulfonates; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects; D005453:Fluorescence; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects; D013748:Tetracaine / Q000494:pharmacology*
D000817:Anilino Naphthalenesulfonates; D002800:Cholinesterase Inhibitors; D008563:Membrane Lipids; D013748:Tetracaine; D000110:Acetylcholinesterase