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At least 667 records · Page 37Linked to original sources
PubMed1991

Effects of quinolone carboxylic acid derivatives on GABAA receptor-mediated stimulation of gastric acid secretion and intestinal motility.

The present study investigates the effects of some quinolone carboxylic acid derivatives on GABAA receptor-mediated excitatory responses in gastrointestinal preparations in vivo and in vitro. In stomach-perfused rats, norfloxacin, nalidixic and pipemidic acid dose dependently antagonized acid hypersecretion induced by muscimol. Under the same conditions, the quinolone derivatives failed to modify acid hypersecretion evoked by 2-deoxy-D-glucose. In the isolated guinea-pig ileum, norfloxacin, nalidixic and pipemidic acid antagonized muscimol-elicited contractions in a non-competitive manner. In contrast, these drugs did not influence ileal cholinergic contractions evoked by transmural electrical stimulation or by exogenous acetylcholine. Taken together, these results suggest that the quinolone derivatives tested act as antagonists at both central and peripheral GABAA receptors. In addition, GABAA-mediated gastrointestinal responses might represent a simple and reliable method to assay the GABAA receptor antagonist properties of new quinolone derivatives.

Acetylcholine↗
PubMed1983

Primary cultures of bovine chromaffin cells synthesize and secrete vasoactive intestinal polypeptide (VIP).

Dispersed cells of the bovine adrenal medulla express immunoreactive vasoactive intestinal polypeptide (VIP) after 24 hours in culture, although VIP could not be detected in extracts of bovine adrenal medulla or cortex. Immunoreactive VIP eluted from a reversed-phrase chromatography column with the same retention time as authentic porcine VIP1-28. VIP in chromaffin cells in culture appears to be contained in a secretory granule pool, since it, like methionine-enkephalin (met-enk) was released into the medium after exposure of cells to nicotine, carbachol, veratridine and elevated potassium in a dose-dependent manner. Dose-response curves for VIP and enkephalin release by the above secretagogues were similar but not identical. Enkephalins and VIP may either be contained in separate subpopulations of chromaffin cells or co-stored in the same cells.

Adrenal Medulla↗
PubMed1985

Intestinal epithelial cells and musculature contain different muscarinic binding sites.

Muscarinic receptors on epithelial cells mediate intestinal secretion, while those in intestinal smooth muscle mediate motility. Experiments were carried out to determine whether the muscarinic receptors mediating each of these two functions in intestinal tissue might be associated with differences in the way agonist and antagonist drugs interact with the receptors. The inhibition constant (Kj) values for atropine, pirenzepine, and oxotremorine competition of specifically bound (3H)QNB were determined using membrane preparations from the muscular coat and from epithelial cells of rat jejunum, ileum, and colon. The Kj values of atropine were similar (1.2-10 nM) when comparing muscle layers and epithelial cells from any intestinal region. In contrast, the Kj values for pirenzepine were significantly higher in membranes from the musculature (400-1,200 nM) than in any of the epithelial cell membranes (20-100 nM). Kj values for pirenzepine in gut muscle were similar to those in heart (300 nM), whereas the Kj values in the cerebral cortex (39 nM) and the epithelial cell membranes closely approximated one another. The Kj values for oxotremorine competition of QNB binding in all intestinal muscular tissues (29-48 nM) and in heart (16 nM) were less than those of the intestinal epithelial cells (100-1,300 nM) or cerebral cortex (71 nM). Thus, pirenzepine and oxotremorine binding studies show that the nature of interactions between these agents and muscarinic sites is different when comparing epithelial cells and musculature of the gut.

Animals↗
PubMed1977

Characterization of the Chinese hamster ovary cell assay for the enterotoxins of Vibrio cholerae and Escherichia coli and for specific antisera, and toxoid.

The morphologic change in Chinese hamster ovary (CHO) cells that is associated with increased intracellular concentrations of adenosine 3':5'-cyclic phosphate (cyclic AMP) provided a highly sensitive assay for the heat-liable enterotoxins of Vibrio cholerae and Escherichia coli. The similarity between the responses of CHO cells and those of intestinal mucosa to enterotoxins was demonstrated by the inhibition of these effects by the ganglioside galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide (GM1), as well as by specific antisera. The antisera against either enterotoxin were more effective in inhibiting the effects of homologous toxin than those of heterologous toxin, but cross-neutralization also occurred in both cases. When choleragenoid, the natural toxoid of cholera toxin, was incubated with the CHO cells, the subsequent effects of the toxin on the morphology of the cells were prevented as were the effects of the toxin on intestinal secretion. However, choleragenoid did not prevent the effects of E. coli toxin. The similarity between the action of enterotoxins on CHO cell morphology and on secretion by the small intestine suggests that there are similar binding sites in these tissues. The potential usefulness of the CHO cell assay in quantitative measurement of antitoxic immunity is thus demonstrated.

Animals↗
PubMed1998

Heterotopic intestinal transplantation aggravates the insult of chronic rejection.

BACKGROUND: Intestinal grafts are placed either heterotopically (out of continuity) or orthotopically (in continuity); the latter is believed to be advantageous, as intraluminal nutrients and intestinal secretions might modulate the intestinal immune status and possibly delay rejection. METHODS: This study was designed to delineate the effects of heterotopic versus orthotopic allograft position on the morphology and function of intestinal smooth muscle in our rat model of chronic rejection. Syngeneic orthotopic grafts were evaluated to control for changes due to the transplantation process. RESULTS: Histochemistry of the graft's muscularis externa showed a significant thickening due to hyperplasia and hypertrophy, which was most pronounced in heterotopic grafts (control = 92+/-2.4 microm, syngeneic grafts = 140+/-6.7 microm, orthotopic allografts = 278+/-26.6 microm, heterotopic allografts = 456+/-50 microm). In terms of function, muscle strips from allografts only generated 23% of the total bethanechol-induced contractile force in vitro compared to unoperated controls and syngeneic grafts. The mean resting membrane potential of control and isograft muscle cells was -69 +/- 0.9 mV with a slow-wave amplitude of 20+/-0.5 mV. Chronic rejection hyperpolarized the resting membrane potential of orthotopic allografts (-66 +/- 0.5 mV) and even more so of heterotopic allografts (-58 +/- 3.4 mV). Slow-wave amplitudes were decreased in orthotopic (14+/-0.9 mV) and nearly abolished in heterotopic allografts (2+/-1.2 mV). CONCLUSIONS: Our data indicate that allografts in heterotopic position are most susceptible to the insult of chronic rejection exemplified by increased proliferative and hypertrophic transformation of intestinal smooth muscle and a marked decrease in mechanical and electrical activity.

Animals↗
PubMed1990

Characterization of an alpha-amidating activity in a human pancreatic tumour secreting vasoactive intestinal peptide (VIP).

A case of watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome due to a pancreatic tumour and identified by VIP plasma level, VIP immunocytochemistry, and ultrastructural analysis of tumour sections, is reported. Since VIP is the mediator of the syndrome and is biologically active under its amidated form, the enzymatic alpha-amidating activity was investigated and characterized in tumour extract; using the synthetic substrate D-Tyr-Val-Gly, the enzyme displayed an optimal activity at pH 7.0, under aerobic conditions and with 35 microM CuSO4 and 3 mM ascorbate as co-factors. The Kmax and Vmax values of the enzymatic activity were 133.7 microM and 26.9 pmol/h/micrograms protein respectively. Its molecular weight, determined by molecular sieving, was close to 36 kDa. Other tumours of the human endocrine pancreas were also investigated for the enzymatic activity. The clinical interest of studying the regulation of the alpha-amidating activity in such tumours is discussed.

Female↗
PubMed1995

Tropisetron and octreotide reduce serotonin-induced fluid hypersecretion in pig jejunum.

In vitro data suggest that the serotonin receptor subtype 4 (5-HT4) mediate part of the serotonin (5-HT)-induced intestinal secretion. This study elucidates the involvement of the intestinal 5-HT4 receptor subtype and the anti-diarrhoeal therapeutic potentials of tropisetron and octreotide in 5-HT-induced intestinal hypersecretion in vivo. The effects of intraluminal 5-HT, 5-methoxytryptamine, and tropisetron (ICS 205-930), and subcutaneous octreotide (SMS 201-995) on fluid hypersecretion (accumulation) was studied in tied-off loops in pig jejunum. 5-HT, 5-methoxytryptamine (5-HT4 agonist), and tropisetron (5-HT3/5-HT4 antagonist) all induced a dose-dependent hypersecretion. Low doses of tropisetron reduced, while high doses of tropisetron enhanced the 5-HT and 5-methoxytryptamine responses. Taking into account the hypersecretory effect by itself, tropisetron seemed to completely block the hypersecretory effects of 5-HT and 5-methoxytryptamine. Finally, octreotide reduced the hypersecretory effect of 5-HT, maximally by 30%. These results suggest the involvement of the intestinal 5-HT4 receptor subtype in 5-HT-induced hypersecretion in pig jejunum in vivo. Furthermore, this study demonstrates a potential therapeutic value for octreotide in 5-HT-related diarrhoeagenic disorders in the pig.

Animals↗
PubMed1995

Proteolytic activity of the Bacteroides fragilis enterotoxin causes fluid secretion and intestinal damage in vivo.

Strains of Bacteroides fragilis that produce an enterotoxin have been implicated in diarrheal disease in farm animals and humans during the past decade. Our laboratory has purified and characterized this enterotoxin as a single polypeptide (M(r), approximately 20,000). Recently, we used PCR to clone and sequence the enterotoxin gene from B. fragilis and showed that it exhibits significant homology with extracellular metalloproteases. Further studies showed that the purified enterotoxin has protease activity. To further characterize the role of this enterotoxin in diarrheal disease, we studied the histological and pathological effects of highly purified B. fragilis enterotoxin in lamb, rabbit, and rat ligated intestinal loops. When the enterotoxin was injected into ligated ileal and colonic loops, there was significant tissue damage and subsequent fluid accumulation. The fluid response in the ileum was greater in lambs than in rabbits and rats, whereas the fluid response in the colon was greater in rabbits than in lambs and rats. Analysis of the intestinal fluid elicited by the enterotoxin revealed an accumulation of chloride and sodium as well as albumin and total protein. Histological examination revealed mild necrosis of epithelial cells, crypt elongation, villus attenuation, and hyperplasia. There was extensive detachment and rounding of surface epithelial cells and an infiltration of neutrophils. Enterotoxic activity was inhibited by the metal chelators EDTA and 1,10-phenanthroline; to some degree, the enterotoxic activity could be reconstituted by the addition of zinc to the chelated enterotoxin. Our results indicate that the enterotoxin elicits a significant fluid response subsequent to tissue damage in the small and large intestine. These data further support the idea that this enterotoxin is an important virulence factor in B. fragilis-associated diarrhea.

Animals↗
PubMed1988

Effects of prostaglandin E2 on disease activity, gastric secretion and intestinal permeability, and morphology in patients with rheumatoid arthritis.

The effects of oral natural prostaglandin E2 (PGE2) on symptoms, disease activity, and gastrointestinal functions in rheumatoid arthritis (RA) were studied in an open pilot trial. Twelve patients, six taking and six not taking non-steroidal anti-inflammatory drugs (NSAIDs), received 1 mg natural PGE2 three times a day for six weeks. The treatment was tolerated well and the only side effect noted was slightly looser stools in three patients. Half of the patients reported subjective improvement and none had aggravation of symptoms. The Ritchie articular index and several biochemical inflammation markers decreased and were significantly reduced at the end of the treatment period. The thickness of the small intestinal mucosa increased during the PGE2 treatment. The intestinal permeability pattern, measured by urinary excretion of polyethylene glycols (PEG 400), differed between the patients taking and not taking NSAIDs. The initially high urinary PEG 400 excretion values in the patients taking NSAIDs decreased and the initially low excretion values in patients not taking NSAIDs increased during the PGE2 treatment. The jejunal contents became sterile in 5/6 patients not taking NSAIDs and remained sterile in 1/6 patients taking NSAIDs at the end of the treatment. The treatment period was associated with a reduction of lactobacilli in patients not treated with NSAIDs. Thus the treatment appeared to decrease disease activity and to improve small intestinal functions in patients with RA, findings that need confirmation in a controlled trial.

Adult↗
PubMed1982

Controlled trial of chlorpromazine as antisecretory agent in patients with cholera hydrated intravenously.

A randomised controlled trial was conducted to investigate the ability of chlorpromazine to reduce intestinal secretion in cholera. Chlorpromazine had reduced loss of intestinal fluid in animals with diarrhoea induced by cholera toxin, and in a preliminary study the drug had reduced purging in patients with cholera. Forty-six adults with cholera were included in the randomised trial. Of these, 34 were treated with chlorpromazine (1 mg/kg or 4 mg/kg either by mouth or intramuscularly) and 12 served as controls. After treatment with the drug there was a significantly greater reduction in the rate of fluid loss in the treated patients than in the controls during the first (p less than 0.005), second (p less than 0.05), and fourth (p less than 0.01) eight-hour periods, but not during the third eight-hour period; the dose of 4 mg/kg was only marginally more effective than 1 mg/kg. The effect of chlorpromazine was strikingly biphasic, with one peak during the first eight hours and another 24-32 hours after administration. Chlorpromazine also significantly reduced the duration of diarrhoea, frequency of vomiting, and amount of intravenous fluid required. The drug induced mild sedation and no hypotension in these well-hydrated patients. These findings confirm the effectiveness of chlorpromazine in reducing fluid loss in cholera. A sedative effect, however, especially in children, may limit its usefulness and requires further study.

Adult↗