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Afferent fibers from gastrointestinal tract outnumber efferents ten times in vagal nerves. Modifying the afferent input makes possible to change discharge of vagal efferents affecting gastrointestinal functions in process known as neuromodulation (NM). Lately it has been used in the treatment of pain and hyperactive neurogenic bladder in urology. MC induced NM may therefore provide a concurrent to pharmacology tool, in treatment of gastrointestinal disorders. The aim of this study was to investigate the effects of long term neuromodulation procedure with use of MC on gastric motility, secretion and weight control in conscious rats. Experiments were performed on 30 Wistar male rats (250—350 g) divided in two groups: sham operated and microsurgically implanted with MC on left vagal nerve below diaphragm. Following stimulation parameters were used: frequency of 0.5—30 Hz, amplitude of 0.55 V, impulse duration of 10 ms in monophasic fashion. In both groups food intake and body weight were measured through the period of 2 weeks after recovery period. Then gastric fistula was implanted in gastric antrum and fasted gastric motility recorded with use of PowerLab system (Australia). Gastric emptying and secretion were also tested with use of phenol red and automatic titration methods. On the daily basis glucose level with standard test and leptin after MC implantation were measured. Recording of vagal activity in fasted rats showed burst of action potentials about 5 ± 2,5 in period of 5000 sec, each burst with spike frequency up to 35 Hz. Food (5 ml of Intralipid – intragastrically) almost doubled amount of bursts to 12 ± 5 in period of 5000 sec with increase in frequency at spike up to 50 Hz. MC induced vagal activity showed continuous spike activity similar to fed pattern. MC induced NM decreases daily food intake by 6% (33.6 ± 4.8 vs control 35.5 ± 4.8 g, p < 0.01). Body weight gain in rats before MC implantation decreased by 20% within 2 weeks after recovery (34.8 ± 9.08 vs control 23.56 ± 4.15 g). Fasting control glucose level also decreased of 5.5% (93.15 ± 9.3 vs control 98.5 ± 11.2 mg%, p < 0.05). Frequency of gastric contractions did not change significantly in MC versus control but amplitude of contractions increased of about 66.7% (2.0 ± 0.8 vs 1.17 ± 0.52) at the dominant frequency 0.08 Hz range and about 71.5% (1.17 ± 0.35 vs 0.68 ± 0.47, p < 0.05) at the frequency 0.12 Hz. in FFT analysis PowerLab (chart v = 4.01). BAO decreased by 29.25% without H+ concentration changes (0.2 ± 0.14 vs 0.14 ± 0.12 mmol/30min, p < 0,05) but MAO did not change in MC rats (0.37 ± 0.25 vs 0.42 ± 0.28 mmol/30min, p0.05). Gastric emptying of isotonic solution increased by 10% (90.46 ± 5.34 vs 80.39 ± 9.95) percent of marker passing to duodenum /5min,.p < 0.0001). Our results suggest that MC induced NM affect brain-gut axis via influencing metabolic and gastric function and decreases body weight. 706
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The effect of orexins on intestinal motility in vitro in fed and fasted rats

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Orexin-A and -B (OXA, OXB) are peptides involved in many gastrointestinal (GI) functions, including motility. Orexins, their precursors and receptors are present in the GI tract. The expression of orexins increases in the hypothalamus and gastrointestinal tract in response to fasting. We have examined the effect of OXA and OXB on GI motility in vitro in fed and fasted rats. The intestinal segments were mounted in chambers filled with Krebs solution. Isotonic contractions were measured in response to acetylcholine (10-5 M), electric field stimulation (EFS), and orexins (10-9-10-7 M) alone or in the presence of orexin-1 type receptor antagonist, SB- 334867 (10-5 M), tetrodotoxin (TTX) 10-6 M, or atropine (10-5 M). Orexins caused a dose-dependent increase of intestinal segment contractions with a more pronounced effect of OXB over OXA. Fasting did not influence orexin-induced responses. Incubation with SB-334867 led to a marked decrease in orexin-induced contractions in OXA-treated segments, while those of OXB were not affected. Atropine diminished contractions only in fasted animals, while TTX led to a decreased response to orexins in both groups. The results show that OXB is predominant in inducing gut motility response, that the effect of orexins is not fully dependent on cholinergic and Na+ transmissions, and that involvement of other transmitters is possible.
This manuscript reviews the current views on morphology and function of the distinct subpopulations of interstitial cells of Cajal (ICC) in the digestive tract and their interrelationships with surrounding cells. Three different functions have been postulated so far, i.e. a pacemaker role, a mediator in enteric excitatory and inhibitory neurotransmission and a mechanosensor. Attention will also be paid to the interstitial cells of Cajal and their possible involvement in pathophysiological conditions. Finally, perspectives for interstitial cells of Cajal as targets for therapeutic intervention will be discussed.
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