Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth muscles.
Tacrine, a non-competitive reversible acetylcholinesterase and butyrylcholineserase inhibitor, caused a concentration-dependent tonic contraction of gastric smooth muscle preparations in the concentration range 1 x 10(-7) mol/L - 1 x 10(-5) mol/L, whereas concentrations higher than 2 x 10(-5) mol/L induced a biphasic effect; a short-time contraction was followed by a prolonged relaxation. To shed some light on the mechanism underlying this untypical relaxation, the amplitude of mechanical reactions caused by tacrine were compared with those of tacrine in the presence of atropine, ipratropium, metrifonate, TTX, nifedipine, D-600, caffeine, apamin, and charybdotoxin. The results obtained revealed that the relaxation was neither cholinergic in nature, nor mediated by the influence of the drug on intramural neuronal structures. It was not influenced by processes inducing changes in cytosolic Ca2+ levels. This assumption was confirmed by experiments with permeabilized muscle preparations that were pre-contracted in a solution with pCa 5.5. Tacrine relaxed the smooth muscles in spite of the constant intracellular Ca2+ concentration resulting from the permeabilization. These findings argue that tacrine at concentrations higher than 2 x 10(-5) mol/L has a desensitizing effect on the contractile apparatus of gastric corpus smooth muscle preparations towards Ca2+.
Krustev
Atanas D
AD
Department of Physics and Biophysics, Medical University, Plovdiv, Bulgaria.
Argirova
Mariana D
MD
Getova
Damianka P
DP
Turiiski
Valentin I
VI
Prissadova
Natalia A
NA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects*; D013619:Tacrine / Q000494:pharmacology*; D013997:Time Factors
D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D002110:Caffeine; D013619:Tacrine; D012964:Sodium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium