Role of muscle tone in peristalsis in guinea-pig small intestine.
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We investigated the involvement of muscle tone and circular muscle (CM) contraction in peristalsis in isolated guinea-pig small intestine. A segment of jejunum (approximately 13 cm) was mounted into a three chambered partitioned bath. Peristaltic waves were initiated in the oral chamber either by: (1) infusing fluid into the oral end of the jejunum; the ejected fluid was diverted via a cannula from reaching the intermediate and anal chambers, or by (2) intraluminal balloon distension of the empty oral segment. Tension of the circular muscle was measured in all three chambers. Peristaltic waves elicited by fluid infusion were evoked at an abrupt threshold. In contrast, peristaltic waves elicited by distension could be graded in amplitude according to stimulus intensity. Peristaltic waves evoked in an empty intestine exhibited similar propagation velocities to peristaltic waves associated with fluid propulsion. Nifedipine (200-400 nM) added to the intermediate chamber to block muscle contraction did not prevent peristaltic waves elicited by either stimulus from propagating into the anal chamber, although their amplitude was attenuated. Nifedipine to the site of stimulation (oral chamber) abolished peristaltic waves generated by either stimulus. Tetrodotoxin (1-2 microM), or a low Ca2+-high Mg2+ solution to the intermediate chamber abolished the propagation of peristalsis from the oral to anal chambers. In conclusion, graded peristaltic waves can occur in an empty intestine. Therefore peristalsis is not necessarily an "all-or-none" phenomenon. Peristalsis depends on the spread of nervous activity along the bowel, rather than the reactivation of neural circuits caused by displacement of fluid in the lumen. However, local muscle tone and contraction are important for the initiation and maintenance of peristaltic propagation. (+info)
Disturbance of peristalsis in the guinea-pig isolated small intestine by indomethacin, but not cyclo-oxygenase isoform-selective inhibitors.
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1. Since the cyclo-oxygenase (COX) isoform-nonselective inhibitor indomethacin is known to modify intestinal motility, we analysed the effects of COX-1 and COX-2 inhibition on intestinal peristalsis. 2. Peristalsis in isolated segments of the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the pressure changes associated with peristalsis. 3. The COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398 (both at 0.1 -- 1 microM) and the isoform-nonselective inhibitors flurbiprofen (0.01 - 10 microM) and piroxicam (0.1 - 50 microM) were without major influence on peristalsis, whereas indomethacin and etodolac (0.1 -- 10 microM) disturbed the regularity of peristalsis by causing nonpropulsive circular muscle contractions. 4. Radioimmunoassay measurements showed that SC-560, NS-398, indomethacin and etodolac (each at 1 microM) suppressed the release of 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)) from the intestinal segments. 5. Reverse transcription - polymerase chain reaction tests revealed that, relative to glyceraldehyde-3 phosphate dehydrogenase ribonucleic acid, the expression of COX-1 mRNA increased by a factor of 2.0 whereas that of COX-2 mRNA rose by a factor of 7.9 during the 2 h experimental period. 6. Pharmacological experiments indicated that the action of indomethacin to disturb intestinal peristalsis was unrelated to inhibition of L-type calcium channels, adenosine triphosphate-sensitive potassium channels or phosphodiesterase type IV. 7. These results show that selective inhibition of COX-1 and COX-2 does not grossly alter peristaltic motor activity in the guinea-pig isolated small intestine and that the effect of indomethacin to disturb the regular pattern of propulsive motility in this species is unrelated to COX inhibition. (+info)
Relationship between esophageal muscle thickness and intraluminal pressure: an ultrasonographic study.
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A number of studies show a close temporal relationship between the rate of change in muscle thickness as detected by high-frequency intraluminal ultrasonography (HFIUS) and intraluminal pressure measured by manometry. There is a marked variability in esophageal contraction amplitude from one swallow to another at a given level in the esophagus and along the length of the esophagus. Furthermore, peristaltic pressures are higher in the distal compared with the proximal esophagus. The goal of this study was to evaluate the relationship between the baseline and peak muscle thickness and the contraction amplitude during swallow-induced contractions along the length of the esophagus. Fifteen normal subjects were studied using simultaneous esophageal pressures and HFIUS or HFIUS alone. Recordings were made during baseline and standardized swallows in the lower esophageal sphincter (LES) and at 2, 4, 6, 8, and 10 cm above the LES. HFIUS images were digitized, and esophageal muscle thickness and peak contraction amplitudes were measured. In the resting state, muscle thickness is higher in the LES compared with the rest of the esophagus. Baseline muscle thickness is also significantly higher at 2 cm vs. 10 cm above the LES. In a given subject and among different subjects, there is a good relationship between peak muscle thickness and peak peristaltic pressures (r = 0.55) at all sites along the length of the esophagus. The positive correlation between pressure and muscle thickness implies that the mean circumferential wall stress is fairly uniform from one swallow to another, irrespective of the contraction amplitude. (+info)
Evidence supporting presence of two pacemakers in rat colon.
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Intracellular microelectrodes and organ bath techniques were used to study spontaneous cyclic electrical and mechanical activity in the rat colon. Electron microscopy and immunohistochemical studies showed two major populations of interstitial cells of Cajal (ICC): one associated with Auerbach's plexus (ICC-AP) and one with the submuscular plexus (ICC-SMP). The ICC-SMP network partly adhered to the submucosa when removed and was generally strongly damaged after separation of musculature and submucosa. Similarly, longitudinal muscle removal severely damaged AP. Two electrical and mechanical activity patterns were recorded: pattern A, low-frequency (0.5--1.5 cycles/min), high-amplitude oscillations; and pattern B, high-frequency (13--15 cycles/min), low-amplitude oscillations. Pattern A was recorded in preparations with intact AP but absent in those without intact AP. Pattern B was recorded in preparations with intact SMP but was absent in those lacking SMP. With full-thickness strips, the superimposed patterns A and B were recorded in circular muscle. When longitudinal muscle mechanical activity was recorded, only pattern A was present. We conclude that two pacemakers regulate rat colonic cyclic activity: the ICC-SMP network (responsible for cyclic slow waves and small-amplitude contractions) and the ICC-AP network (which may drive the cyclic depolarizations responsible for high-amplitude contractions). This is the first report showing consistent slow wave activity in the rodent colon. (+info)
Neural regulation of in vitro giant contractions in the rat colon.
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The rat middle colon spontaneously generates regularly occurring giant contractions (GCs) in vitro. We investigated the neurohumoral and intracellular regulation of these contractions in a standard muscle bath. cGMP content was measured in strips and single smooth muscle cells. The circular muscle strips generated spontaneous GCs. Their amplitude and frequency were significantly increased by tetrodotoxin (TTX), omega-conotoxin, N(omega)-nitro-L-arginine (L-NNA), and the dopamine D(1) receptor antagonist Sch-23390. The GCs were unaffected by hexamethonium, atropine, and antagonists of serotonergic (5-HT(1--4)), histaminergic (H(1--2)), and tachykininergic (NK(1--2)) receptors but enhanced by NK(3) receptor antagonism. The guanylate cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ) also enhanced GCs to the same extent as TTX and L-NNA, and each of the three agents prevented the effects of the others. GCs were abolished by electrical field stimulation, S-nitroso-N-acetyl-penicillamine, and 8-bromo-cGMP. BAY-K-8644 and apamin enhanced the GCs, but they were abolished by D-600. Basal cGMP content in strips was decreased by TTX, L-NNA, or ODQ, but these treatments had no effect on cGMP content of enzymatically dissociated single smooth muscle cells. We conclude that spontaneous contractions in the rat colonic muscle strips are not generated by cholinergic, serotonergic, or histaminergic input. Constitutive release of nitric oxide from enteric neurons sustains cGMP synthesis in the colonic smooth muscle to suppress spontaneous in vitro GCs. (+info)
Simultaneous intracellular recordings from longitudinal and circular muscle during the peristaltic reflex in guinea-pig distal colon.
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1. Simultaneous intracellular recordings were made from longitudinal muscle (LM) and circular muscle (CM) cells of guinea-pig distal colon during the peristaltic reflex. 2. Spontaneous rhythmical depolarizations with superimposed action potentials (mean amplitude: 19 +/- 2 mV) were regularly recorded from the LM (mean interval: 7 +/- 1 s). In contrast, in the CM layer, spontaneous action potentials occurred with an irregular frequency. Although spontaneous action potentials in LM were rarely correlated in time with those in CM, spontaneous inhibitory junction potentials (sIJPs) were found to occur synchronously in both muscles (5 out of 27 animals; 19 %). 3. Graded inflation of an intra-luminal balloon or mucosal stimulation oral to the recording electrodes elicited gradeable compound IJPs synchronously in both LM (mean amplitude: 6 +/- 1 mV) and CM (mean amplitude: 9 +/- 1 mV) (descending inhibitory reflex). Evoked IJPs were often followed by action potentials in both muscle layers. 4. Mucosal stimuli applied anal to the recording electrodes elicited compound excitatory junction potentials (EJPs) synchronously in both muscles layers that were often associated with the generation of action potentials. In the LM, evoked EJP amplitudes ranged from 3 mV (subthreshold) to 31 mV (including the action potential) and in the CM from 4 mV (subthreshold) to 44 mV (including the action potential). 5. Apamin (500 nM) reduced the evoked IJP in the CM by 55 % (from 11 +/- 2 to 5 +/- 1 mV), but caused no significant reduction in the LM layer (from 8 +/- 1 to 6 +/- 1 mV). Apamin-resistant IJPs in both muscle layers were likely to be due to nitric oxide, since they were abolished by L-NA (100 microM). 6. Atropine (1 microM) abolished the ascending excitatory reflex in both muscles. 7. Injection of neurobiotin into the LM and CM confirmed that simultaneous intracellular recordings were made from different muscle layers. 8. In conclusion, during the peristaltic reflex, the LM and CM layers receive synchronous inhibitory neuromuscular inputs during descending inhibition and synchronous excitatory neuromuscular inputs during ascending excitation. No evidence was found to support reciprocal innervation. (+info)
The pharmacokinetics of the novel promotile drug, tegaserod, are similar in healthy subjects-male and female, elderly and young.
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BACKGROUND: Tegaserod (HTF 919) is a selective 5-HT4 receptor partial agonist in development for the treatment of irritable bowel syndrome. AIM: This study aimed to assess the effect of age and gender on the single-dose pharmacokinetics of tegaserod. METHODS: In a parallel-group, open-label study, a single dose of tegaserod (12 mg) was administered to four groups of healthy young male, young female, elderly male and elderly female subjects (n=10 per group). Blood samples were collected from 0 to 24 h postdose. Non-compartmental pharmacokinetics evaluation and statistical analysis (ANOVA and Wilcoxon signed ranks test for tmax) were performed. RESULTS: Tegaserod was well tolerated in all groups. There was no effect of age or gender on tmax and Cmax. Gender did not affect AUC0-infinity and AUC0-tz; there was a statistically significant effect of age on these parameters. AUC0-infinity and AUC0-tz in the elderly were greater than in the young (AUC0-infinity ratio 1.37, P < 0.001; AUC0-tz ratio 1.23, P=0.029). This increase in exposure is judged not to be clinically relevant because it is within the variability in the pharmacokinetics parameters of tegaserod and because the dose-response relationship of tegaserod is relatively shallow. CONCLUSIONS: No dose adjustment for age or gender is recommended in tegaserod therapy. (+info)
Luminal morphology of the avian lower intestine: evidence supporting the importance of retrograde peristalsis for water conservation.
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Tissue from the lower intestine of two species of sparrow, the house sparrow Passer domesticus and savannah sparrow Passerculus sandwichensis was sectioned in an unbiased manner and examined quantitatively using stereology. The tissue was processed for light microscopy, and scanning and transmission electron microscopy to examine the extent to which microvilli enhanced the epithelial surface area of the cecae, rectum, and coprodeum. Parameters measured included individual microvillus surface area, microvilli packing density, and absolute surface area. In both species, the average surface area, packing density, and absolute surface area of microvilli decreased distally along the rectum and coprodeum. All three measured variables were not statistically significant (P > 0.05) between species. Surface area amplification on the cecae due to microvilli was low, and approximated values equivalent to distal regions of the rectum and coprodeum. In the cecae, microvilli within the savannah sparrow had a significantly higher (P < 0.05) individual surface area, packing density, and absolute surface area than in the house sparrow. The functional implications of a change in microvilli population are discussed in relation to retrograde peristalsis within the lower intestine of birds. (+info)