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+.
Ursolic acid (UA) in concentrations of 1×10-7 mol/L-5×10-5 mol/L induced relaxation in gastric smooth muscle (SM) tissues, in a concentration-dependent manner. The relaxation did not change membrane potential and slow wave contraction patterns. A significant decrease in amplitude and frequency of spikepotentials was observed. UA-induced reactivity was removed when SM preparations were treated with nifedipine (1×10-6 mol/L). Ca 2+-induced contractions of the depolarized SM preparations (42 mmol/L K + ; Ca 2+-free Krebs solution) were substantially reduced in the presence of UA. It was determined that, in certain concentrations, UA influenced L-type Са 2+ channels, and reduced the Ca 2+ influx.
Most of the side effects induced by tacrine are associated with the gastrointestinal (GI) tract. The aim of the study was to analyze the nature of radiographically registered, tacrine-induced changes in evacuatory function, as well as to find a possible correlation with the immediate in vitro action of the drug on smooth muscles from the GI tracts of rats. The tacrine dose we used reliably delayed GI passage: contrast matter was not fully evacuated, predominantly from the stomach and cecum. The delay resulted from changes in tone and peristaltic activity, specific for the various regions of the tract. These changes were associated with a superposing of the responses due to the anticholinesterase and noncholinergic action of tacrine.
Citation: Saracheva KE, Prissadova NA, Turiiski VI, Slavchev VI, Krastev AD, Getova DP. Effects of the novel high-affi nity 5-HT(1B/1D)-receptor ligand frovatriptan on the rat carotid artery.Folia Medica 2017;59(1): 31-36. doi: 10.1515/folmed-2017-0006 Background: In blood vessels 5-HT stimulates sympathetic nerves, the endothelium and vascular smooth muscle cells. Triptans are specifi c anti-migraine drugs and they activate the serotoninergic 5HT1b/d receptors causing vasoconstriction of the cerebral vessels. Aim: To evaluate the eff ect of frovatriptan on isolated rat carotid artery. Methods: Contractile activity of the preparations was registered isometrically. Krebs solution (pH = 7.4) was used for washing smooth muscle (SM) preparations aerated with 95% O 2 and 5% CO 2 at 37°C. The 60-minute adaptation of tone level of preparations was taken as a starting tone and the changes such as contraction or relaxation were calculated using it. Results: Frovatriptan (1×10 -6 mol/l -1×10 -5 mol/l) induced a contraction, but at higher concentrations it caused relaxation of the carotid artery. The L-norepinephrine contractile reaction was enhanced in the presence of frovatriptan. In the presence of 5-HT2 receptor antagonist, methysergide, frovatriptan increased the relaxation. In the presence of the specifi c α-1 receptor antagonist, prazosin, the frovatriptan-induced relaxation decreased. Conclusion:The observed contractile eff ect of frovatriptan is probably associated with the main eff ect of the drug -activation of the serotoninergic 5HT 1B /1D receptors causing vasoconstriction of the cerebral vessels and their anti-migraine eff ect. At higher concentrations, frovatriptan, most likely via some non-specifi c mechanism, could activate the following intracellular chain reaction: stimulation of α 1D could activate eNOS which may increase in the concentration of NO which results in the fi nal eff ect of relaxation. BACKGROUND
Background: Besides its “classical” neurotransmitter function in the central and peripheral nervous systems, serotonin, or 5-hydroxytryptamine (5-HT) is also a local hormone in a number of tissues, including those of the GI tract. Radiation is known to be able to disrupt certain functions of the tract, modulated by 5-HT-signaling pathways, or the serotonin receptors themselves. Aim: The present investigation focused on clarifying the nature and extent of influence of an accelerated electron beam with energy of 9 MeV on the serotonergic mediation of healthy smooth muscle gastric tissue of rats following total body irradiation of the animals. Materials and methods: The study involved a control group and two experimental groups of animals exposed to 1 and 5 Gy, respectively, using Siemens Primus S/N 3561. Circular smooth muscle tissues were isolated from rats 1 hour and 18 hours after they were exposed to 1 and 5 Gy and also 5 days after irradiation from the rats that received a dose of 5 Gy in order to investigate the action of exogenous serotonin at increasing concentrations from 10-8 to 10-4 mol/l. The contractile reactivity of each group SM preparations was registered isometrically. Results: Electron beams with energy of 9 MeV did not damage the contractile apparatus of gastric SM of rats and had a stimulating effect on contractility resulting from rapidly developing processes (1 hour) or later occurring once (5 days). Conclusions: Difference was observed in the importance of the factors of received dose, lapse of time from irradiation to investigation of SM tissues, and exogenous 5-HT concentration for the changes in SM reactivity in serotonin-induced tonic and phasic responses.
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