Delayed Evacuatory Function due to Specific Smooth Muscle Reactivity in the Gastrointestinal Tracts of Tacrine-Treated Rats

Krustev, A.; Sirakov, Vladimir N.; Turiiski, Valentin I.; Getova, D.; Velkova, K; Prissadova, N.

doi:10.1159/000107969

Cited by 1 publication

(2 citation statements)

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“…Numerous studies have shown that cholinesterase inhibitors stimulate the contractile activity of isolated gastric smooth muscles (SM) [9] and the motility of gastrointestinal (GI) tract [10][11][12] by raising the level of endogenous acetylcholine, which is a main excitatory neurotransmitter for the tract. Tacrine is not an exception to this rule.…”

Section: Introductionmentioning

confidence: 99%

“…It is a result from the direct action of tacrine over the contractile apparatus of the gastrointestinal smooth muscles [14]. When applied in vivo (daily dose 0.5 mg/kg) the drug significantly influences the motility of GI tract, causing hypotension, inhibited peristaltic activity and retarded evacuatory kinetics [12,16]. This influence, untypical of acetylcholinesterase inhibitors, indicates a significant presence of non-anticholinesterase mechanisms in the formation of the total drug effect and most likely accounts for its specific side effects on GI tract motility [12,16,17].…”

Section: Introductionmentioning

confidence: 99%

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Participation of cAMP in tacrine-induced gastric smooth muscle relaxation

et al. 2010

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Tacrine, a well-known acetylcholinesterase inhibitor, applied in concentrations higher than 2×10-5 mol/l promoted Ca 2+ -independent relaxation of rat gastric smooth muscles in experiments in vitro. The relaxation was not cholinergic and was a result of influence of tacrine over intracellular signaling pathways regulating smooth muscle contraction/relaxation. The nature of this untypical muscle relaxation was studied by using smooth muscle strips isolated from rat stomach. Their bioelectrical and mechanical responses were recorded after treatment with tacrine and different activators or blockers of intracellular pathways involved in muscle contractility. Following the activation of adenylate cyclase with 1×10 -6 mol/l forskolin and increase in the concentration of cyclic adenosine monophosphate (cAMP) after application of 4×10 -5 mol/l SQ22536, a significant decrease in the muscle relaxation was observed. Theophylline (2×10 -4 mol/l), a phosphodiesterase inhibitor, had no effect on the amplitude of tacrine-induced relaxation. The latter was also reduced by inhibition of protein kinase A (PKA) with 5×10 -6 mol/l KT5720. These findings support the assumption that tacrine promoted smooth muscle relaxation through PKA-induced phosphorylation and inhibition of myosin light chain kinase activity. The reduction of spike-linked Ca 2+ influx provoked by tacrine was probably a secondary contributing process, associated with an influence of increased cAMP level on Ca 2+ channels.

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Section: Introductionmentioning

confidence: 99%