title: Sensitizing effect of tacrine on M-cholinergic receptors in gastric smooth muscle of rats.
abstract: OBJECTIVE
  To find if tacrine exerts a sensitizing effect on the cholinergic receptors of gastric smooth muscles, and study some of the mechanisms inducing it and measure the relative intensity of tacrine's effects on contractile activity.
  
  
  METHODS
  Isometric recording of the mechanical activity of gastric smooth muscle preparations; determination of acetyl-cholinesterase activity in smooth-muscle tissue homogenates using Ellman's method.
  
  
  RESULTS
  We found that the threshold concentration for tacrine not reducing the acetylcholinesterase activity and not having an effect on the smooth muscle preparations was 1 x 10(-8) mol/l. This concentration, however, significantly increased the acetylcholine-induced contraction compared with the controls, after the smooth-muscle tissue was incubated for 60 or 100 min. Treating smooth-muscle preparations with tacrine in a concentration of 5 x 10(-6) mol/l triggered a contraction induced by the drug's anti-cholinesterase activity. A secondary contraction was induced after 38.6 +/- 5.6 min. There was no secondary contraction after the control acetylcholine-induced effect. Atropine (1 x 10(-6) mol/l) inhibits this effect. Preliminary treatment of smooth muscle preparations with hexamethonium (1 x 10(-6) mol/l) did not change significantly the intensity of the first phase of tacrine-induced contraction and shifted in time the appearance of the second contractile phase.
  
  
  CONCLUSIONS
  Tacrine has a sensitizing effect on M-cholinergic receptors; it occurs after a long incubation of the gastric smooth muscles with the drug and is manifested as a secondary contraction which is shifted in time and is significantly inhibited by atropine.
authors.affiliation: Department of Biophysics, Medical University, Plovdiv, Bulgaria. p_natali@abv.bg
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Prisadova
authors.forename: Raina G
authors.initials: RG
authors.lastname: Ardasheva
authors.forename: Valentin I
authors.initials: VI
authors.lastname: Turiiski
authors.forename: Mariana D
authors.initials: MD
authors.lastname: Argirova
authors.forename: Damyanka P
authors.initials: DP
authors.lastname: Getova
authors.forename: Atanas D
authors.initials: AD
authors.lastname: Krustev
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects* / Q000502:physiology; D013619:Tacrine / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D013619:Tacrine; D000109:Acetylcholine