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Tacrine-induced tachyphylaxis in gastric smooth muscles

  • Research Article
  • Published:
Central European Journal of Biology

Abstract

Tacrine is a medication applied in cases of mild to moderate dementia in Alzheimer’s disease. By blocking acetylcholinesterase activity the drug increases the concentration of acetylcholine, whose effects influence the functions of different organs and systems of the body. The effect of tacrine on smooth muscle preparations isolated from rat stomach was studied by isometric registration of muscle contractility. Our investigations found a specific significant systematic decrease in the strength of consecutive tacrine-induced contractions of smooth muscle preparations, a phenomenon known as tachyphylaxis. The tacrineinduced tachyphylaxis was significantly inhibited by SQ22536 (inhibitor of adenylate cyclase activity), by blockers of nitric oxide synthase and KT5823 (inhibitor of protein kinase G). The process was not influenced by cyclopiazonic acid (specific blocker of sarco/endoplasmic reticulum Ca2+-ATPase,) and atropine (blocker of M-cholinergic receptors). We hypothesize that the overlapping and different time-development of the two opposing processes: smooth muscle contraction caused by acetylcholinesterase inhibition and tacrine-induced relaxation influenced by synthesis of nitric oxide, results in tachyphylaxis.

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Abbreviations

AC:

adenylate cyclase

CNS:

central nervous system

GC:

guanylyl cyclase

GI:

gastrointestinal tract

MLCPK:

myosin light chain protein kinase

NOSs:

nitric oxide synthases

PKG:

protein kinase

SM:

smooth muscles

SERCA:

sarcoplasmic Ca2+ pump

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Authors and Affiliations

  1. Department of Biophysics, Medical University, 4002, Plovdiv, Bulgaria

    Natalia A. Prissadova, Athanas D. Kristev, Valentin I. Turiiski & Raina I. Ardasheva

  2. Department of Pharmacology, Clinical Pharmacology and Drug Toxicology, Medical University, 4002, Plovdiv, Bulgaria

    Daminka P. Getova

  3. Department of Chemistry and Biochemistry, Medical University, 4002, Plovdiv, Bulgaria

    Mariana D. Argirova

Authors
  1. Natalia A. Prissadova
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  2. Athanas D. Kristev
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  3. Daminka P. Getova
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  4. Mariana D. Argirova
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  5. Valentin I. Turiiski
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  6. Raina I. Ardasheva
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Correspondence to Natalia A. Prissadova.

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Prissadova, N.A., Kristev, A.D., Getova, D.P. et al. Tacrine-induced tachyphylaxis in gastric smooth muscles. cent.eur.j.biol. 7, 1013–1020 (2012). https://doi.org/10.2478/s11535-012-0103-7

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  • DOI: https://doi.org/10.2478/s11535-012-0103-7

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