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Relationship between mast cell degranulation and jejunal myoelectric alterations in intestinal anaphylaxis in rats.

The effects of two degranulators of mast cells and intestinal anaphylaxis on jejunal myoelectric activity were compared in rats fasted for 15 hours. Attempts to antagonize the motility changes were performed using antagonists of histamine and serotonin and a cyclooxygenase and lipoxygenase inhibitor. Hooded Lister rats were chronically fitted with electrodes implanted in the jejunal wall. A group of rats was sensitized to egg albumin and challenged 14 days later by intraduodenal infusion of antigen. Sensitized animals had serum titers greater than or equal to 1:64. The other group was administered with mast cells degranulators. Both 48/80 (1 mg/kg), a degranulator of connective mast cells, and bromolasalocid (2 mg/kg), acting on connective and mucosal mast cells, induced a phase of total spiking inhibition followed by a progressive irregular spiking activity until the recovery of migrating myoelectric complex pattern (about 3 hours after injection). In contrast, antigen challenge disrupted the migrating myoelectric complex pattern, which was replaced by a peculiar pattern characterized by propagated spike burst, lasting 98 +/- 11.3 minutes. Chlorpheniramine (1 mg/kg) antagonized only the inhibitory phase induced by degranulators and was ineffective on the intestinal anaphylaxis-induced motor changes. Methysergide (1 mg/kg) and indomethacin (5 mg/kg) significantly reduced the degranulator effects as well as the anaphylaxis-induced alterations of intestinal motility. It is concluded that anaphylaxis-induced motor disturbances are relevant to mucosal mast cell degranulation involving 5-hydroxytryptamine and arachidonic acid derivative products, whereas histamine release appears to be a minor component.

Anaphylaxis↗

Extremely low electrical current generated by porcine small intestine smooth muscle alters bacterial autolysin production.

The effect of extremely low electrical currents, identical to those generated by the gut smooth muscle, on bacterial autolysin production in vitro was tested in the present study. When stimulated with these electrical currents, the bacteria Pediococcus pentosaceus 16:1 produced groups of peptidoglycan hydrolases that differed from those produced by the unstimulated (control) bacteria. The autolysins synthesized by the P. pentosaceus 16:1 under extremely low electrical currents were effective against peptidoglycans from the cell walls of various lactic acid bacteria strains, whereas the autolysins from the control bacteria acted exclusively against P. pentosaceus 16:1 cell walls. Thus, it can be predicted that in vivo the electrical currents generated by the intestinal smooth muscles, which can be recorded as the myoelectrical migrating complexes, could regulate lactic acid bacteria strain growth in the gut.

Animals↗

Gut myoelectrical activity induces heat shock response in Escherichia coli and Caco-2 cells.

The heat shock response is associated with the intracellular expression of a number of highly conserved heat shock proteins (Hsps). According to their molecular size, Hsps have been divided into several groups, which are strongly conserved and show high homology between the species, e.g., Hsp70, MW 70 kDa (Lindquist & Craig, 1998; Morimoto, 1998; Jolly & Morimoto, 2000; Zylicz et al. 2001). In all organisms the Hsp expression under stress conditions is regulated at transcriptional level, e.g., in humans by the heat shock transcription factor Hsf1 (Morimoto, 1998; Wu, 1995), while in Escherichia coli by replacement of the sigma factor sigma(70) in RNA polymerase by the sigma factor sigma(32) (Gross, 1987). The Hsps allow cell survival under stress conditions by renaturating of denaturated proteins, protecting of stress-labile proteins, preventing protein aggregation (chaperone functions), and by degradation of damaged proteins (protease activities) (Lindquist & Craig, 1988; Morimoto, 1998; Jolly & Morimoto, 2000). They have also many housekeeping functions under non-stressful conditions during the cell cycle, growth, development, and differentiation (Morimoto, 1998). Among a number of plausible inducing factors already studied, extremely low artificial electromagnetic fields have been shown to induce stress response in various cells, such as expression of sigma(32) mRNA (Cairo et al. 1998) and induction of DnaJ and DnaK proteins in Eschericha coli (Chow & Tung, 2000); expression of hsp-16 gene in Caenorhabditis elegans (Miyakawa et al., 2001); induction of heat shock transcription factor Hsf1 and Hsp70, Hsp90 and Hsp27 in human cells (Lin et al. 1997; Lin et al. 1998; Goodman & Blank, 1998; Pipkin et al. 1999). Nevertheless, the role of endogenous electromagnetic fields, i.e., generated by electrically active cells within a body remains controversial. Heat shock proteins (Hsps) protect cells against various environmental and endogenous stressors. Cytoprotection caused by Hsps involves tolerance induced by one agent against other, more severe agents. We have found that exposure of prokaryotic (Escherichia coli) and eukaryotic (Caco-2) cells to an electrical field (EF) connected with a myoelectrical migrating complex (MMC) generated by the small intestine smooth muscle induces the heat shock response. Using Western blot analysis, we have detected an elevated level of sigma factor 32 in E. coli cells exposed to MMC-related EF, and confocal microscopy indicated an increased level of the inducible form of Hsp70 protein in EF-stimulated Caco-2 cells. Additionally, we have found that this induced level of Hsp70 protected the Caco-2 cells against apoptosis caused by camptothecin. Our observations suggest that the myoelectrical activity of the gut may induce heat shock mechanisms in the cells of gut epithelium as well as in gastrointestinal micro-organisms.

Action Potentials↗

Effect of the electrical currents generated by the intestinal smooth muscle layers on pancreatic enzyme activity: an in vitro study.

Gut enzymes in the small intestine are exposed to extremely low electrical currents (ELEC) generated by the smooth muscle. In the present study, the in vitro tests were undertaken to evaluate the effect of these electric currents on the activity of the proteolytic pancreatic digestive enzymes. A simulator generating the typical electrical activity of pig gut was used for these studies. The electric current emitted by the simulator was transmitted to the samples, containing enzyme and its substrate, using platinum plate electrodes. All samples were incubated at 37 degrees C for 1 h. The changes in optical density, corresponding to enzyme activity, in samples stimulated for 1 h with ELEC was compared with that not exposed to ELEC. The obtained results show that the electrical current with the characteristics of the myoelectrical migrating complex (MMC) has an influence on pancreatic enzyme activity. Increased endopeptidase and reduced exopeptidase activity was noticed in samples treated with ELEC. This observation can be of important as analyzed factors which can alter enzymatic activity of the gut, can thus also affect feed/food digestibility.

Animals↗

Influence of intestinal myoelectrical activity on the growth of Escherichia coli.

Intestinal bacteria, particularly those adhering to intestinal epithelial cells, are exposed to electric fields and currents generated by the muscular activity of the small intestine. This activity displays a regular pattern known as the myoelectrical migrating complex (MMC). In order to explore the possibility that these endogenous electric fields could affect bacterial growth, a digitised duodenal signal obtained via serosal electrodes from a healthy calf was recorded and then applied via platinum electrodes to Escherichia coli cultures. The culture tubes were placed within a Faraday shield, incubated at 37 degrees C with shaking, and stimulated by the electric current for 5 or 8 h. The growth of E. coli stimulated by the electric current was significantly altered compared to those of non-stimulated controls: after a period of intensive growth, inhibition of cell division was observed. This was not the case when the bacteria with lon mutation were used. Moreover, synchronic bacterial culture could not be achieved in the presence of the MMC-related electric field. These results suggest that the myoelectrical activity of the duodenum, through action on cell membrane, can affect cell division of intestinal bacteria.

Animals↗

[Electromyographic profile of the human jejunum after abdominal surgery].

The purpose of this work was to describe the electromyographical profile of the jejunum observed after various types of abdominal operations. The electromyogram of the first 140 centimeters of the small intestine was recorded on a continuous basis by an intraluminal tube between the 6th and 20th day after abdominal surgery in twenty patients. Results allow us to describe a profile of the patient's intestinal electromyogram after abdominal surgery. It was characterized by three consecutive periods: a) early reappearance of migrating myoelectric complexes occurring during the first period; b) a very short second period beginning immediately before the expulsion of gases; during this period the electrical activity fluctuated and appeared disorganised; c) finally, during the third period, after gas expulsion, peristaltic rushes were associated with normalized migrating myoelectrical complexes. Both early and permanent migrating myoelectrical complexes characterize the normal postoperative period. Continuous linear integration of the jejunal electromyogram might be a useful tool for the monitoring of postoperative intestinal motility as a routine procedure.

Abdomen↗

Nitric oxide is involved in the inhibitory action of cholecystokinin octapeptide (CCK-OP) on proximal colonic motility.

To determine whether nitric oxide (NO) is a possible mediator in the inhibitory action of CCK-octapeptide (CCK-OP) on circular muscle contractions of the rat proximal colon, contractile activities of the circular muscle were recorded in the proximal colon of unrestrained conscious rats in the fasting state using a miniature strain gauge force transducer and an implantable telemetry system. Regular and rhythmic phasic contractions were observed during the fasted condition, similar to the myoelectric migrating complex seen in intestinal contractions of the fasting dog. These phasic contractions were almost completely inhibited after intraperitoneal (i.p.) administration of CCK-OP at a dose of 15 microg/kg body weight. N(omega)-nitro-arginine, methyl ester (L-NAME), at doses of 20 and 200 mg/kg i.p. administered prior to i.p. injection of CCK-OP, prevented the inhibitory action on the fasting phasic contractions. The degree of prevention was dose-dependent. 100 mg/kg body weight i.p. injection of L-arginine inhibited the circular muscle contractions. The same dose of D-arginine had no action on contractions of the circular muscle of the proximal colon in the fasted rat. From these data, we conclude that NO is one possible mediator in the inhibitory mechanism of CCK-OP on smooth muscle motor activity of the rat proximal colon in vivo.

Animals↗

Exposure of Escherichia coli to intestinal myoelectrical activity-related electric field induces resistance against subsequent UV(254 nm) (UVC) irradiation.

Survival of Escherichia coli K-12 AB1157 irradiated with UVC (UV(254 nm)) was enhanced after pre-treatment with a low-tension electric field (EF). The EF used was identical to the electrical field generated by the small intestine (myoelectrical migrating complex--MMC), registered in a healthy calf and transmitted into the memory of an EF generator. The EF emitted by the generator was transmitted via electrodes placed in shaken bacterial cultures. The protective effects of the EF on the E. coli survival after exposure to UV were: (i) observed only for the dnaJ(+)dnaK(+) strain, and not for the DeltadnaJdnaK heat shock mutant; (ii) strictly dependent on the temperature at which the bacteria were grown; (iii) most obvious when the bacteria were incubated at 37 degrees C. Moreover, the MMC-related EF and a higher temperature (40 degrees C) show a similar protective effect against UV-irradiation. The results point to the involvement of the heat shock response in the low-tension EF-induced protection of bacterial cells against UVC-irradiation. Additionally, treatment with the MMC-related EF affects total protein contents and their pattern in E. coli cells. The EF-treatment did not show any influence on the level of the argE3(ochre) --> Arg(+) reversions.

Animals↗

Vasoactive intestinal peptide and substance P receptor antagonists improve postoperative ileus.

Octreotide, a somatostatin analogue that inhibits the release of most gut peptides, hastens the resolution of experimental postoperative ileus, suggesting that gut peptides mediate this process. We studied the role of two gut peptides involved in the control of normal gut motility, vasoactive intestinal peptide (VIP), and substance P (SP), in the initiation and maintenance of postoperative small bowel ileus in rats by preoperative administration of VIP and SP receptor antagonists, (VIP-ra and SP-ra). Thirty male Sprague-Dawley rats (300-350 g) underwent laparotomy. One half underwent placement of a duodenal catheter for transit studies while the other half had serosal electrodes placed on the proximal jejunum for myoelectric recordings. Six days later, animals were separated into three treatment groups of five each. Control animals were pretreated with ip saline, while the others received either VIP-ra or SP-ra prior to standardized laparotomy. Following abdominal closure, [Na51]CrO4 was injected into the duodenum and the animals were sacrificed 25 min later. The small bowel was then excised and divided into 10 equal segments. Small bowel transit was calculated as the geometric center of [Na51]CrO4 distribution. The interval until the return of migrating myoelectric complexes (MMCs) was determined in animals with intestinal electrodes. VIP-ra-treated rats demonstrated a 67% improvement in the geometric center of radiolabel relative to controls and SP-ra-treated rats had a 23% improvement (3.67 +/- 0.06 VIP-ra vs 2.69 +/- 0.09 SP-ra vs 2.20 +/- 0.09 control, P < 0.01). MMCs returned 180 +/- 17 min in controls vs 99 +/- 14 min in VIP-ra-treated rats (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intestinal neuromuscular function after preservation and transplantation.

While it is well known that prolonged preservation of the intestinal graft causes severe mucosal damage after transplantation, little is known about the effect on neuromuscular function. The entire small intestine of adult hound dogs was flushed and preserved with cold lactated Ringer's solution and autotransplanted either immediately (n = 6) or after 24 hr (n = 6). Animals undergoing sham operation (n = 4) were used as a control. Fasting motility and the response of the intestinal smooth muscle and enteric nerves to bethanechol (100 microg/kg/0.5 hr, iv) and cisapride (0.5 mg/kg, iv) were determined by a multiple strain gauge method on Postoperative Days 2,4,7,14,21, and 28. Compared to the control, immediately transplanted grafts and those preserved for 24 hr developed delayed reappearance of migrating myoelectric complexes (MMC), hypercontractile activity, and reduced response to bethanechol and cisapride administration. Animals in the preservation group developed more abnormal fasting motility after transplantation, but responses to bethanechol and cisapride stimulation were not markedly different from those of the immediate group. The reappearance of MMC occurred 3 weeks postoperatively in the preservation group compared to 2 days in the immediate group. The results of our study indicate that intestinal dysmotility is augmented in prolonged-preservation grafts compared to those with brief preservation. The dysmotility was transient and normalized 3 to 4 weeks after surgery. Preservation and reperfusion injury to the neuromuscular system of intestinal grafts are reversible and are attenuated by simple hypothermia.

Animals↗

Intraduodenal cholecystokinin octapeptide (CCK-8) can stimulate pancreatic secretion in the calf.

The effect of CCK-8 administered into the duodenal lumen and into the systemic blood on pancreatic secretion and duodenal migrating myoelectric complex (MMC) was studied in four calves. Simultaneous MMC recordings and collections of pancreatic juice were performed on valves that had been fasted overnight. Intraduodenal (0, 100, and 300 pmol/kg body wt) and intravenous (0, 30, and 100/pmol kg) infusions of CCK-8 were made for 5 min during the no spiking activity (NSA) phase of duodenal MMC associated with a nadir of periodic pancreatic secretion. CCK-8 was also administered during continuous atropine infusion (5 micrograms/kg/min). Both intraduodenal and intravenous infusions of CCK-8 resulted in marked pancreatic responses in juice outflow, bicarbonate output, and protein output. Atropine decreased pancreatic response (protein output) to intravenous CCK-8 and markedly inhibited the response (juice flow, bicarbonate, and protein output) to intraduodenal CCK-8. Infusions of CCK-8 did not affect the duration of MMC in the duodenum. Plasma CCK increased significantly after intravenous infusion, but remained unchanged after intraduodenal infusion. In conclusion, CCK-8 can stimulate pancreatic secretion from the duodenal lumen, possibly via a cholinergic mechanism in the calf.

Animals↗

[The physiology of intestinal pouches].

To summarize, J-shaped and W-shaped ileal pouches serve as adequate neorectal reservoirs after proctocolectomy. These pouches anastomosed directly to the anal canal are as distensible and capacious and as readily evacuated as the rectum in health. However, the use of S- or H-shaped ileal pouches, which have efferent limbs positioned between the pouch and the anal canal, sometimes leads to outflow obstruction and incomplete evacuation. There is little doubt that neorectums made of ileum can allow patients to have entirely "normal" patterns of fecal continence. Nonetheless, with pouch distension, large-amplitude, propulsive pouch contractions occur. These large pressure waves bring on the urge to defecate. They stress the anal sphincters more acutely than either the infrequent, small-amplitude, nonpropulsive contractions or clustered contractions of the healthy rectum. Nonetheless, patients learn to recognize the different signals heralding the impending need for evacuation from the ileal pouch and deal with them. Jejunal pouches, because of their greater distensibility and larger capacity, and the greater frequency of interdigestive migrating myoelectric complexes (MMCs) occurring in them, hold the promise of being a better rectal substitute than ileal pouches. They are more difficult to construct, however. Colonic pouches, when anastomosed to the anal canal after rectal resection, also act as adequate fecal reservoirs. Their main drawback is the inability of some patients to empty them. Small (5 cm) colonic pouches seem to empty better than larger (10-15 cm) ones. Jejunal pouches and colonic segments used as gastric substitutes after gastrectomy provide a better reservoir for ingested food than straight jejunal segments. The main drawback of the pouches is their inability to triturate the solid content of a meal and to regulate the rate of its emptying into the small intestine. Liquids and solids likely empty from these pouches at the same rate, in contrast to the slower emptying rate of solids from the healthy stomach. This likely leads to maldigestion of solids, perhaps contributing to the weight loss often found after gastrectomy.

Colorectal Neoplasms↗

Influence of postoperative epidural analgesia with bupivacaine on intestinal motility, transit time, and anastomotic healing.

Epidural application of bupivacaine has been suggested to have a sympatholytic effect on spinal reflex mechanisms that shortens postoperative paralysis and leads to an improved transit time. The influence on anastomitic healing remains controversial. Laparotomy was performed in eight dogs. A short segment of the distal colon was resected and five electrodes were fixed on the serosa to measure the myoelectric activity (e.g., Migrating Myoelectric Complex--MMC). After operation a peridural catheter was placed between L7 and the sacral crest. One milliliter of bupivacaine 0.25% for each 3 kg of body weight was injected every 4 hours. Barium pellets coated in wax were placed into the stomach to allow radiographic representation of transit time. After 5 days the colon anastomosis was resected to measure the bursting pressure. In the peridural analgesia group (PDA) we found one small bowel intussusception and one covered anastomotic leakage. Postoperative PDA led to early and severe myoelectric activity but did not influence the time until the first MMC occurred (44 +/- 0.8 h, PDA; 44.6 +/- 1.5 h,control). Neither the transit time to the colon (50.2 +/- 1.9h, PDA; 51.7 +/- 5.5 h, control) nor the anastomotic healing was influenced (bursting pressure: 176 +/- 21.1 mmHg, PDA; 152 +/- 27.7 mmHg, control). Postoperative epidural analgesia with bupivacaine shortens intestinal paralysis. Early myoelectric activity with a lack of propulsive activity can cause complications like small bowel intussusception. Hence early postoperative enteral nutrition after epidural analgesia is risky. Because the influence of epidural analgesia on propulsive motility remains unclear, it seems reasonable to recommend its limited use in colon surgery.

Analgesia, Epidural↗

Does selective vagotomy prevent delayed gastric emptying and altered myoelectric activity following Roux-en-Y gastrojejunostomy?

Delayed gastric emptying occurs frequently following Roux-en-Y gastrojejunostomy. The role of vagal denervation in the etiology of this "Roux-stasis syndrome" is controversial. This study evaluates the effect of selective vagotomy on gastric emptying and motility following Roux-en-Y. Four dogs underwent control gastric emptying studies. The animals then underwent selective vagotomy, antrectomy, and Billroth II gastrojejunostomy, with placement of serosal electrodes. Gastric emptying was assessed with simultaneous myoelectric recordings, and the animals were converted to Roux-en-Y, followed by repeat studies. Gastric emptying was unchanged following selective vagotomy, antrectomy, and Billroth II gastrojejunostomy (T 1/2: 132 +/- 18 min [SEM] versus 118 +/- 14 min control) but was markedly delayed following Roux-en-Y diversion (T 1/2: 286 +/- 44 min; p less than 0.01). All animals went into the fed pattern following Billroth II gastrojejunostomy (migrating myoelectric complex [MMC] interval: 326 +/- 6 min postprandial versus 92 +/- 5 min fasting; p less than 0.01), but no fed pattern was recognized in three of four animals following Roux-en-Y diversion (MMC interval: 68 +/- 12 min postprandial versus 62 +/- 1.5 min fasting; p = NS). In a canine model, selective vagotomy does not prevent delayed gastric emptying or myoelectric alterations following Roux-en-Y.

Anastomosis, Roux-en-Y↗

The impact of jejunal transplant peristalsis on enteric flora.

The importance of phase III of the migrating myoelectric complex (MMC) for homeostasis of enteric flora is well documented. The goal of this study was to evaluate in an isogeneic rat model the effect of MMC changes on the self-purging capacity of the jejunal graft. The proximal 25% of the entire jejunoileum of Lewis rats was transplanted orthotopically. Electrodes were then fixed to the graft. Native bowel of five rats and five rats with analogue jejunal segmentation served as controls. Myoelectric recordings were carried out until day 21, when animals were killed for bacteriologic analysis of the segments analyzed myoelectrically and the of neighboring gut. MMCs were observed in all animals during all recordings. Phase III was irregular in transplants because of long-lasting periods of phase III absence alternating with phase III occurring more frequently. The variation coefficient of phase III periodicity calculated for grafts was 48.74, for native bowel 14.79, and for segmented jejunum 22.9. Enteric flora found in all specimens consisted of colonic-like microorganisms. Titers of microorganisms in grafts did not differ from control segments. These findings show that phase III periodicity is severely altered in jejunal grafts. Homeostasis of enteric flora, however, is not influenced by the transplant procedure.

Animals↗

Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome.

The long acting somatostatin analogue octreotide acetate has been effective in the treatment of early dumping syndrome. We hypothesized that this may be related to its effects on inhibiting gastric emptying and delaying intestinal transit. To study the effect of octreotide acetate on intestinal motility in patients we carried out a randomized, double-blinded study using a subcutaneous injection of either octreotide acetate (100 micrograms) or placebo given 20 min prior to ingestion of a high carbohydrate "dumping" meal in six patients with known severe dumping syndrome. Prior to each study a multilumen polyethylene tube was inserted into the efferent limb to study small intestinal contractions using low compliance pneumo-hydraulic water-perfused manometry. Octreotide acetate prevented dumping symptoms in all six patients and induced the appearance of migrating myoelectric complexes (MMC) characteristic of interdigestive motility. After ingestion of the dumping meal the postprandial "fed" motility pattern lasted for 141 +/- 9 min while after octreotide acetate the fed motility lasted for 29 +/- 5 min (P less than 0.03). The vigor of the fed motility pattern as measured by the motility index (MI = loge (sum of amplitudes X No. of contractions + 1] was lower after octreotide acetate than after placebo (15.1 +/- 0.1 vs 13.4 +/- 0.2, P less than 0.03). The induction of fasting MMC motility pattern and reduction in the duration and vigor of fed motility may explain the symptomatic relief these patients obtained with octreotide acetate. It is not known whether the induction of the MMC is a direct effect of octreotide acetate or secondary to the concomitant inhibition of peptide release (neurotensin, insulin, glucagon, pancreatic polypeptide) that has been demonstrated in earlier studies.

Dumping Syndrome↗

Gastric emptying and myoelectric activity following Roux-en-Y gastrojejunostomy.

The purpose of this study was to compare gastric emptying and Roux myoelectric activity in a canine model. Four dogs underwent truncal vagotomy, antrectomy, and 40 cm Roux-en-Y gastrojejunostomy, with placement of serosal electrodes. Following recovery, gastric emptying was determined scintigraphically with a radiolabeled solid meal, and fasting and fed small-bowel myoelectric activity was obtained. Gastric emptying was markedly slowed compared to control unoperated animals (202 +/- 91 versus 46 +/- 12 min; P less than 0.05). Slow wave frequency declined in the Roux limb compared to the duodenum (14.2 +/- 0.4 versus 18.0 +/- .06 counts per minute; P less than 0.01). No gradient in slow wave frequency was observed in the Roux limb, although one animal was noted to have reversed propagation of slow waves in the proximal Roux limb. Migrating myoelectric complexes (MMCs) were coordinated between the Roux limb and jejunum distal to the enteroenterostomy, but not with the duodenum. Periodicity of the MMCs was different in the Roux limb and duodenum (98.6 +/- 6.3 versus 138 +/- 17.5 min; P less than 0.05). None of the animals converted to the fed myoelectric pattern with a 272 kcal meal (MMC periodicity in the Roux limb = 99 +/- 10 min postprandially, P = N.S.). These quantitative and qualitative alterations in myoelectric activity may contribute to the observed delay in gastric emptying following Roux-en-Y gastrojejunostomy.

Anastomosis, Roux-en-Y↗

Oral administration of Tyr-MIF-1 stimulates gastric emptying and gastrointestinal motility in rodents.

The effects of orally administered Tyr-MIF-1, an agonist of an endogenous antiopiate system, were examined on gastric emptying in mice and gastrointestinal myoelectric activity in rats. Tyr-MIF-1 (5 mg/kg in mice, 20 mg/kg in rats) accelerated gastric emptying of a methylcellulose test meal, increased the frequency of antral spike bursts, and disrupted intestinal migrating myoelectric complexes. These effects were reproduced by a subcutaneous administration of Tyr-MIF-1 at the same dosage. They were blocked by naloxone (1 mg/kg) but not by the kappa receptor subtype antagonist MR 2266 (1 mg/kg). The GABAA antagonist bicuculline (0.5 mg/kg), but not the GABAB antagonist 2-hydroxysaclofen (4 mg/kg), also antagonized the effects of Tyr-MIF-1. These data demonstrate that oral Tyr-MIF-1 stimulates gastric emptying and gastrointestinal motility through a systemic or central action that involves opioid and GABA systems.

Administration, Cutaneous↗