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At least 325 records · Page 18Linked to original sources
PubMed2007

Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes.

Heme induces Cl(-) secretion in intestinal epithelial cells, most likely via carbon monoxide (CO) generation. The major source of endogenous CO comes from the degradation of heme via heme oxygenase (HO). We hypothesized that an inhibitor of HO activity, tin protoporphyrin (SnPP), may inhibit the stimulatory effect of heme on Cl(-) secretion. To test this hypothesis, we treated an intestinal epithelial cell line (Caco-2 cells) with SnPP. In contrast to our expectations, Caco-2 cells treated with SnPP had an increase in their short-circuit currents (I(sc)) in Ussing chambers. This effect was observed only when the system was exposed to ambient light. SnPP-induced I(sc) was caused by Cl(-) secretion because it was inhibited in Cl(-)-free medium, with ouabain or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). The Cl(-) secretion was not via activation of the CFTR, because a specific inhibitor had no effect. Likewise, inhibitors of adenylate cyclase and guanylate cyclase had no effect on the enhanced I(sc). SnPP-induced I(sc) was inhibited by the antioxidant vitamins, alpha-tocopherol and ascorbic acid. Electron paramagnetic resonance experiments confirmed that oxidative reactions were initiated with light in cells loaded with SnPP. These data suggest that SnPP-induced effects may not be entirely due to the inhibition of HO activity but rather to light-induced oxidative processes. These novel effects of SnPP-photosensitized oxidation may also lead to a new understanding of how intestinal Cl(-) secretion can be regulated by the redox environment of the cell.

Antioxidants↗
PubMed2000

Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion.

To explain the very high frequency of cystic fibrosis (CF) mutations in most populations of European descent, it has been proposed that CF heterozygotes have a survival advantage when infected with Vibrio cholerae or Escherichia coli, the toxins of which induce diarrhea by stimulation of active intestinal chloride secretion. Two assumptions underlie this hypothesis: (1) chloride conductance by the CF transmembrane conductance regulator (CFTR) is the rate-limiting step for active intestinal chloride secretion at all levels of expression, from approximately zero in patients with CF to normal levels in people who are not carriers of a mutation; and (2) heterozygotes have smaller amounts of functional intestinal CFTR than do people who are not carriers, and heterozygotes therefore secrete less chloride when exposed to secretagogues. The authors used an intestinal perfusion technique to measure in vivo basal and prostaglandin-stimulated jejunal chloride secretion in normal subjects, CF heterozygotes, and patients with CF. Patients with CF had essentially no active chloride secretion in the basal state, and secretion was not stimulated by a prostaglandin analogue. However, CF heterozygotes secreted chloride at the same rate as did people without a CF mutation. If heterozygotes are assumed to have less-than-normal intestinal CFTR function, these results mean that CFTR expression is not rate limiting for active chloride secretion in heterozygotes. The results do not support the theory that the very high frequency of CF mutations is due to a survival advantage that is conferred on heterozygotes who contract diarrheal illnesses mediated by intestinal hypersecretion of chloride.

Adolescent↗
PubMed2000

Somatostatin through its specific receptor inhibits spontaneous and TNF-alpha- and bacteria-induced IL-8 and IL-1 beta secretion from intestinal epithelial cells.

Intestinal epithelial cells secrete proinflammatory cytokines and chemokines that are crucial in mucosal defense. However, this secretion must be tightly regulated, because uncontrolled secretion of proinflammatory mediators may lead to chronic inflammation and mucosal damage. The aim of this study was to determine whether somatostatin, secreted within the intestinal mucosa, regulates secretion of cytokines from intestinal epithelial cells. The spontaneous as well as TNF-alpha- and Salmonella-induced secretion of IL-8 and IL-1beta derived from intestinal cell lines Caco-2 and HT-29 was measured after treatment with somatostatin or its synthetic analogue, octreotide. Somatostatin, at physiological nanomolar concentrations, markedly inhibited the spontaneous and TNF-alpha-induced secretion of IL-8 and IL-1beta. This inhibition was dose dependent, reaching >90% blockage at 3 nM. Furthermore, somatostatin completely abrogated the increased secretion of IL-8 and IL-1beta after invasion by Salmonella. Octreotide, which mainly stimulates somatostatin receptor subtypes 2 and 5, affected the secretion of IL-8 and IL-1beta similarly, and the somatostatin antagonist cyclo-somatostatin completely blocked the somatostatin- and octreotide-induced inhibitory effects. This inhibition was correlated to a reduction of the mRNA concentrations of IL-8 and IL-1beta. No effect was noted regarding cell viability. These results indicate that somatostatin, by directly interacting with its specific receptors that are expressed on intestinal epithelial cells, down-regulates proinflammatory mediator secretion by a mechanism involving the regulation of transcription. These findings suggest that somatostatin plays an active role in regulating the mucosal inflammatory response of intestinal epithelial cells after physiological and pathophysiological stimulations such as bacterial invasion.

Caco-2 Cells↗
PubMed1997

Differential stimulation of intestinal mucin secretion by cholera toxin and carbachol.

Cholinergic stimulation triggers the secretion of apically stored, preformed mucin from goblet cells but the pathway of cAMP-stimulated mucin secretion is not known. In this study the effect of cholera toxin on mucin secretion in the human colonic goblet cell line HT-29/B6 was investigated and compared to the action of carbachol. PAS staining of mucin blotted onto nitrocellulose served to quantify the secretion of total mucin. Metabolic labelling was used to evaluate the secretion of newly synthesized mucin. The mucinous nature of the detected material was confirmed with an immunoblot employing a well-characterized polyclonal antibody reacting with MUC2-mucin. Cholera toxin caused a 116-fold increase of intracellular cAMP and strongly stimulated the secretion of both preformed and newly synthesized mucin for more than 20 h. Carbachol only triggered the release of preformed mucin immediately after addition. The secretory response to cholera toxin could be partly inhibited by the protein kinase A inhibitor H8 and the microtubule inhibitor colchicine. The action of carbachol was not affected by these agents. In conclusion, we demonstrate a direct cAMP-dependent effect of cholera toxin on mucin secretion by intestinal goblet cells. In contrast to carbachol, the action of cholera toxin involves de novo synthesis of mucin molecules and microtubule-mediated secretion. There seem to be distinct secretion pathways for muscarinic or cAMP-dependent stimulation of mucin secretion.

Calcium↗
PubMed1994

Octreotide in the treatment of refractory diarrhoea and intestinal fistulae.

Persistent, refractory diarrhoea continues to be an important clinical problem. The mechanisms involved are associated with reduced intestinal absorption and increased intestinal secretion. Reduced intestinal absorption can result from small intestinal resection or from disorders in which there is damage to the small intestine. Motility disorders may also impair absorptive function. The rationale for using octreotide in refractory diarrhoea, intestinal motility disorders, and fistulae relates to its ability to promote intestinal absorption and inhibit gastric, pancreatic, and intestinal secretion. Several clinical studies in patients with short bowel syndrome have reported a reduction of intestinal output in patients taking octreotide compared with controls. Additionally, a number of studies have shown that octreotide improves secretory diarrhoea resulting from neuroendocrine tumours, intestinal infections in AIDS patients, and intestinal graft v host disease. Octreotide may be of use in patients suffering from intestinal motility disorders such as those associated with systemic sclerosis. Octreotide may also be of value in promoting closure of gastrointestinal and pancreatic fistulae.

Chronic Disease↗
PubMed1975

[Simultaneous determination of gastric emptying and bile and pancreatic enzyme secretion].

Intestinal perfusion methods with a nonabsorbable marker allow an exact quantitative determination of intestinal absorption and secretion provided that methodological pitfalls are avoided. A modified technique is applied to the simultaneous measurement of biliary and pancreatic secretion during and depending on emptying of a mixed test meal. A duodenal segment was perfused with an isotonic polyethyleneglycol solution (PEG). Reinjection of duodenal aspirates maintained a normal enterohepatic circulation of bile acids (interruption less than 10%). The perfusion was performed in healthy volonteers over a period of 12 to 24 hours, with three mixed formula meals containing 51CrCl3 as a marker ingested at conventional feeding hours. Influence of meal size was studied by means of a high caloric (40 Kcal/b. wt. per day) test meal. Patients with cholesterol gallstones and cirrhosis of the liver only received one formula test meal of 300 Kcal. Instead of concentrations output of trypsin, lipase, bile acids and cholesterol (the latter corrected for duodenal absorption) was calculated from the dilution of PEG in the duodenal juice and gastric emptying was determined by following quantitatively the flow of 51CrCl3. Gastric emptying can be expressed by a single exponential function over most of the time. Only the last 60-100 Kcals were expelled by the stomach at a faster rate. The daily biliary and pancreatic secretion depend indirectly on the amount of food ingested. But during the day light hours (with continuous meal flow), secretion was similar in high and low caloric subjects, while a significant difference became obvious during night hours corresponding to differences in gastric emptying time. Mean hourly output of bile acid, biliary cholesterol, trypsin and lipase is independent from meal size and secretion of pancreatic enzymes reaches the values close to those after maximal stimulation by i.v. CCK-PZ. Output of pancreatic enzymes does not differ in health and gallstone disease or cirrhosis of the liver respectively. Since during digestion in normals approximately one forth of the bile acid pool is secreted hourly into the gut, the number of daily enterohepatic cycles of bile acids can be calculated by 4-6. Patients with cholesterol gallstones maintain normal bile acid output by enhanced cycling of the small pool: An average of 50% of the pool passed the duodenum per hour. A decreased bile acid pool is also present in cases of advanced cirrhosis of the liver. However, hourly output of bile acids in these patients is significantly less than in mild cirrhosis (with normal bile acid pool) or normal controls. Therefore the hourly fraction of the pool secreted is similar to healthy subjects. These findings provide an important information to explain abnormalities in bile acid metabolism in cirrhosis.

Adult↗
PubMed1998

Lipoprotein secretion by intestinal Caco-2 cells is affected differently by trans and cis unsaturated fatty acids: effect of carbon chain length and position of the double bond.

The effects of trans fatty acids on intestinal lipoprotein secretion were determined in polarized Caco-2 cells. Palmitic acid (16:0), palmitoleic acid (c-16:1delta9), and palmitelaidic acid (t-16:1delta9), as well as stearic acid (18:0), oleic acid (c-18:1delta9), c-vaccenic acid (c-18:1delta11), elaidic acid (t-18:1delta9), and t-vaccenic acid (t-18:1delta11) were studied. Compared with 18:0 (control), c- and t-18:1delta9 increased triacylglycerol secretion (2.7- and 3.6-fold, respectively) as well as apolipoprotein (apo) B-48 and apo B-100 secretion (both 1.6-fold compared with 18:0); c- and t-18:1delta11 caused a modest 1.7-fold increase in triacylglycerol secretion with no significant effect on secretion of apo B. Thus, the position of the double bond in the 18:1 isomers, but not its geometrical configuration, affected lipoprotein secretion by Caco-2 cells. In contrast, the effects of the geometrical isomers (cis and trans) of C16 fatty acids were not comparable: t-16:1delta9 did not affect triacylglycerol and apo B secretion (compared with 16:0, as control) whereas c-16:1delta9 was a potent stimulator of secretion of triacylglycerol (2.4-fold higher than 16:0), apo B-48 (1.3-fold higher than 16:0), and apo B-100 (1.5-fold higher than 16:0). We conclude that the carbon chain length of fatty acids, as well as the position of double bonds and their stereochemical configuration, are important determinants of the unique effects of various species of dietary trans fatty acids on lipoprotein secretion and composition in Caco-2 cells.

Caco-2 Cells↗
PubMed1984

Regulation of intestinal goblet cell secretion. III. Isolated intestinal epithelium.

Cholinergic secretagogues evoke mucus secretion from goblet cells in the crypts of small and large intestinal mucosa in vivo and in organ culture. It was not known whether this response reflected a direct action on epithelial cell receptors or an indirect effect involving intermediate neurons of the enteric nervous system. To resolve this, carbachol was applied to isolated intestinal epithelium maintained in vitro. Intact sheets of epithelium, measuring 10-200 mm2, were isolated from the ileum and colon of adult rats following short intravascular perfusion with 30 mM EDTA. The isolated epithelia lacked a basal lamina and cytoplasmic blebs formed on the basal cell surfaces, but cell ultrastructure was normal and intercellular junctions were intact. Autoradiography revealed that both goblet and columnar cells continued to incorporate [3H]glucosamine into nascent secretory macromolecules for at least 45 min after isolation. When exposed to 20 microM carbachol for 5 min, crypt goblet cells discharged their stored mucin granules by compound exocytosis, whereas goblet cells in portions of the epithelium derived from villi or mucosal surfaces were unresponsive. We conclude that cholinergic secretagogues act directly on crypt epithelial cells to elicit mucus secretion.

Animals↗
PubMed1990

Effects of heat-stable Escherichia coli enterotoxin on intestinal alkaline secretion and transepithelial potential difference in the rat intestines in vivo.

The effects of the heat-stable enterotoxin of Escherichia coli (STa) on intestinal alkaline secretion and transepithelial electric potential difference (PD) were investigated in vivo in denervated segments of rat jejunum, ileum, and proximal colon. STa caused a significant increase in alkaline secretion in the jejunum but not in the ileum or colon. The jejunal effect of STa may be ascribed to a stimulation of bicarbonate secretion and/or an inhibition of Na+/H+ exchange. With regard to PD, STa caused a marked rise in colonic PD, whereas only a small response was found in the jejunum. No effect on PD was seen in the ileum. Hexamethonium (10 mg/kg intravenously) significantly diminished the effects of STa on PD, whereas only a small inhibition of the STa-induced alkaline secretion was observed. The effect of lidocaine on PD and alkaline secretion was found to be similar to that of hexamethonium. Atropine had no effect on any of the studied variables. These findings suggest that STa exerts, via nerves, a profound influence on the jejunal transport mechanisms responsible for the changes in PD, whereas the influence on alkaline secretion is to a large extent not mediated via enteric nerves. Thus, the extent of enteric nervous control of epithelial function differs for different transport functions. The findings also indicate that the bicarbonate ion is not the anion mainly responsible for the fluid secretion elicited by STa.

Animals↗
PubMed1988

Elevated serum IgA associated with immunoproliferative enteropathy of Basenji dogs: lack of evidence for alpha heavy-chain disease or enhanced intestinal IgA secretion.

Immunoglobulin isotypes in serum and intestinal secretions of Basenji dogs with chronic diarrhea, asymptomatic Basenji dogs, and healthy control dogs were quantitated and their molecular sizes characterized to detect alpha-chain, gamma-chain, or mu-chain fragments. Quantitation of immunoglobulin isotypes in serum showed that affected Basenjis have significantly elevated serum IgA values as compared to asymptomatic Basenjis and normal control dogs. However, IgA concentrations in intestinal wash fluids were not significantly different for the three groups. Immunoelectrophoresis (IEP) and polyacrylamide gel electrophoresis (PAGE) demonstrated that virtually all IgA was in the dimeric form. Using IEP and immunoselection, we were unable to detect evidence for the presence of alpha-chain or other heavy-(H)-chain fragments. Hyperimmune serum obtained from rabbits immunized with serum or a globulin fraction of affected Basenjis also failed to detect H-chain fragments. The results of this study indicate that immunoproliferative enteropathy of Basenjis resembles closely the nonsecretory form of human immunoproliferative small intestinal disease (IPSID).

Animals↗
PubMed1978

Gut-associated IgA deficiency in lepromatous leprosy.

Sera, intestinal secretions and intestinal biopsies were collected from twelve biopsy-proved lepromatous leprosy patients with the help of a capsule invented by Roy Choudhury. Sera from another twenty-five proved lepromatous cases were also included. Sera and intestinal aspirates from twenty-five normal subjects and twenty patients with intestinal tuberculosis were also taken as controls. Acid-fast organisms, morphologically resembling Mycobacterium leprae, were detected in the intestinal aspirates of only two leprosy patients. Immunoglobulin levels in their sera and elevation secretions were estimated by the single radial immunodiffusion technique. Significant elevation of serum IgG, IgA and IgM, selective IgA deficiency in intestinal aspirates and flattening of intestinal villi along with mononuclear cell infiltration were conspicuous observations in the leprosy group. On the other hand, the patients with intestinal tuberculosis showed elevation of the IgG level in serum as well as in the intestinal secretions. It was postulated that persistent challenge by M. leprae or its antigens to the IgA immunocytes of the intestinal epithelium might have induced tolerance leading to IgA deficiency and subsequent subtotal atrophy of the intestinal villi in the patients with lepromatous leprosy.

Adult↗
PubMed1996

IL-4 enhances IEC-6 intestinal epithelial cell proliferation yet has no effect on IL-6 secretion.

Intestinal epithelial cells (IEC) form an important line of defence at the intestinal mucosa by providing a barrier to lumenal contents and also by their ability to secrete various inflammatory cytokines. Recently, several T cell-derived cytokines have been shown to regulate specific IEC functions. In this study, the effect of IL-4 on IEC proliferation and secretion of the inflammatory cytokine IL-6 was investigated using the non-transformed rat IEC-6 intestinal epithelial cell line. Recombinant rat (rr)IL-4 was found to enhance IEC-6 cell proliferation over 4 days of culture, and this enhancement was dose-dependent. Further studies using specific antibodies confirmed that IL-4 induced the effect and that the effect was not mediated by autocrine-produced transforming growth factor-alpha. However, IL-4 did not induce IL-6 secretion by the IEC-6 cells, nor did it alter IL-1 beta-induced IL-6 secretion. These results indicate that T cells may be capable of regulating IEC proliferation via the secretion of IL-4 without altering the capacity of the IEC to function in the inflammatory response by secreting IL-6.

Animals↗