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At least 1,747 records · Page 97Linked to original sources
PubMed1993

Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop.

Incretins are intestinal factors that stimulate postprandial insulin secretion in preparation for subsequent rises in plasma levels of ingested nutrients. Glucose-dependent insulinotropic peptide (GIP), a duodenal endocrine peptide, is ideally located for such a function. In contrast, the intestinal proglucagon-derived peptide (PGDP), truncated GLP-1 [GLP-1(7-37) or tGLP-1] is equipotent to GIP in insulinotropic activity, but due to its localization in the distal ileum, appears to be poorly situated to fulfill an incretin role in response to direct nutrient stimulation. Despite its distribution, rapid increments in plasma levels of tGLP-1 have been noted in response to nutrient ingestion. We have recently reported that GIP (but not other nutrient-stimulated duodenal endocrine peptides) can stimulate intestinal PGDP secretion in vitro, and therefore hypothesized that GIP might regulate secretion of the intestinal PGDPs, including tGLP-1, in response to nutrient ingestion in vivo in the rat. Placement of either fat or glucose directly into the ileal lumen was demonstrated to significantly stimulate secretion of the intestinal PGDPs (P < 0.05), whereas fat or glucose in the duodenal lumen significantly increased plasma levels of GIP (P < 0.05). In addition, however, duodenal fat treatment also increased the secretion of intestinal PGDPs into the circulation (P < 0.05), with levels rising to same extent as observed after direct administration of fat into the ileum. The rise in plasma GIP levels in response to duodenal fat treatment occurred slightly before the increments in intestinal PGDP levels, suggesting a relationship between the two peptides. Intravenous infusion of GIP to give concentrations similar to those observed after duodenal fat administration induced a 2-fold increase in plasma levels of intestinal PGDPs that was independent of glycemic levels (P < 0.05). No increment in intestinal PGDPs was found in response to infusion of another duodenal endocrine peptide, cholecystokinin. Thus, these data demonstrate a specific effect of GIP to stimulate secretion of the intestinal PGDPs in vivo in the rat. This enteroendocrine loop between the duodenal peptide GIP and the ileal PGDPs may account for some of the early rises in secretion of tGLP-1 observed in response to nutrient ingestion.

Animals↗
PubMed1989

Vasoactive intestinal polypeptide stimulates cholecystokinin secretion in perfused rat duodenum.

We examined the effect of vasoactive intestinal polypeptide (VIP) on cholecystokinin (CCK) secretion from the isolated perfused rat duodenum. VIP stimulated CCK secretion mono-phasically in a concentration-dependent manner in concentrations ranging from 10(-9) to 10(-7) M, and 10(-7) M of VIP led to an increment of 82 +/- 25.8 fmole/3 min. The stimulatory effect of VIP on CCK was not inhibited by 10(-5) M atropine. These results suggest that VIP may directly stimulate CCK secretion from the duodenum and work as a non-cholinergic, peptidergic neurotransmitter.

Animals↗
PubMed1991

Substance P but not vasoactive intestinal peptide modulates immunoglobulin secretion in murine schistosomiasis.

Neuropeptides including SP and VIP modulate Ig secretion by in vitro stimulated lymphocyte cultures. It is not known whether these neuropeptides effect the B cell directly, or if they significantly alter humoral immune responses to pathogens. We have previously shown that granulomas derived from schistosome-infected mice contain immunoglobulin secreting B cells (ISC) as well as eosinophils that secrete substance P (SP) and vasoactive intestinal peptide (VIP). It therefore seemed plausible that B cells derived from infected animals might respond to these neuropeptides, and that such responses might effect immunoregulatory signals. In this study, we addressed these issues in the murine Schistosoma mansoni model, at the level of immunoglobulin secretion in single B cells. Spontaneous ISC were observed in both splenic and granuloma cell preparations. The addition of SP resulted in a dose-dependent reduction in the number and size of plaques (a 50% reduction was observed at 10(-9) M). This effect was blocked with SP antagonists. Similar results were observed in T cell-depleted cell cultures. VIP had no effect on ISC number or plaque size. We conclude that SP, but not VIP, decreases spontaneous ISC number and Ig secretion in short-term cultures of spleen and granuloma cells. SP appears to exert its effects at the level of single B cells through a receptor-mediated mechanism and may thus play an immunoregulatory role in schistosomiasis.

Animals↗
PubMed1999

Enteropathogenic E. coli attenuates secretagogue-induced net intestinal ion transport but not Cl- secretion.

Enteric bacterial pathogens often increase intestinal Cl- secretion. Enteropathogenic Escherichia coli (EPEC) does not stimulate active ion secretion. In fact, EPEC infection decreases net ion transport in response to classic secretagogues. This has been presumed to reflect diminished Cl- secretion. The aim of this study was to investigate the influence of EPEC infection on specific intestinal epithelial ion transport processes. T84 cell monolayers infected with EPEC were used for these studies. EPEC infection significantly decreased short-circuit current (Isc) in response to carbachol and forskolin, yet 125I efflux studies revealed no difference in Cl- channel activity. There was also no alteration in basolateral K+ channel or Na+-K+-2Cl- cotransport activity. Furthermore, net 36Cl- flux was not decreased by EPEC. No alterations in either K+ or Na+ transport could be demonstrated. Instead, removal of basolateral bicarbonate from uninfected monolayers yielded an Isc response approximating that observed with EPEC infection, whereas bicarbonate removal from EPEC-infected monolayers further diminished Isc. These studies suggest that the reduction in stimulated Isc is not secondary to diminished Cl- secretion. Alternatively, bicarbonate-dependent transport processes appear to be perturbed.

Absorption↗
PubMed1988

The effect of splanchnic nerve stimulation and neuropeptide Y on cholera secretion and release of vasoactive intestinal polypeptide in the feline small intestine.

The effect of sympathetic nerve stimulation and intra-arterial infusion of neuropeptide Y (NPY) on net fluid secretion and release of vasoactive intestinal polypeptide (VIP) was studied in the cat small intestine during a secretion due to cholera toxin. Activation of the splanchnic nerves (4 Hz, 5 ms, 5 V) decreased net fluid secretion to 57 +/- 10% of control. Concomitantly, the release of VIP was reduced to less than 50%. Furthermore, close i.a. infusion of NPY (estimated increase in plasma concentration 75 nmol l-1) reduced the net fluid secretion and VIP release to 27 +/- 5 and 28 +/- 4% of the pre-stimulatory value. The correlation between the decrease in net fluid secretion and reduction in VIP release showed a strong positive correlation (r = 0.83). These results strongly indicate that the antisecretory effect of sympathetic nerve stimulation during cholera diarrhoea is mediated by inhibition of secretory VIP neurons in the intestinal mucosa. A similar mechanism is also proposed for the intravascularly administered NPY.

Animals↗
PubMed1999

Water and electrolyte absorption and secretion in the small intestine.

The use of gene-knockout mice permits an increased insight into the role of specific transport proteins and membrane receptors in epithelial water and electrolyte transport. Data on the secondary coupling of water transport to Na-glucose cotransport and the mechanism of action of a number of prosecretory and proabsorptive enteric neurotransmitters are reviewed. Nitric oxide and some experimental treatments with therapeutic potential for cholera toxin-induced water and electrolyte secretion are discussed. A putative role of uroguanylin in intestinal bicarbonate secretion is explored.

Journal Article↗
PubMed2003

Interplay between nitric oxide and vasoactive intestinal polypeptide in inducing fluid secretion in rat jejunum.

Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) interact in the regulation of neuromuscular function in the gut. They are also potent intestinal secretogogues that coexist in the enteric nervous system. The aims of this study were: (1) to investigate the interaction between NO and VIP in inducing fluid secretion in the rat jejunum, and (2) to determine whether the NO effect on intestinal fluid movement is neurally mediated. The single pass perfusion technique was used to study fluid movement in a 25 cm segment of rat jejunum in vivo. A solution containing 20 mM L-arginine, a NO precursor, was perfused into the segment. The effect of the NO synthase inhibitors (L-NAME and L-nitroindazole (L-NI)) and the VIP antagonist ([4Cl-D-Phe6,Leu17]VIP (VIPa)) on L-arginine-induced changes in fluid movement, expressed as microl min(-1) (g dry intestinal weight)(-1), was determined. In addition, the effect of neuronal blockade by tetrodotoxin (TTX) and ablation of the myenteric plexus by benzalkonium chloride (BAC) was studied. In parallel groups of rats, the effect of L-NAME and L-NI on VIP-induced intestinal fluid secretion was also examined. Basal fluid absorption in control rats was (median (interquartile range)) 65 (45-78). L-Arginine induced a significant fluid secretion (-14 (-20 to -5); P<0.01). This effect was reversed completely by L-NAME (60 (36-65); P<0.01) and L-NI (46 (39-75); P<0.01) and partially by VIPa (37 (14-47); P<0.01). TTX and BAC partially inhibited the effect of L-arginine (22 (15-32) and 15 (10-26), respectively; P<0.05). The effect of VIP on fluid movement (-23 (-26 to -14)) was partially reversed by L-NAME (24 (8.4-35.5); P<0.01) and L-NI (29 (4-44); P<0.01). The inhibition of VIP or NO synthase prevented L-arginine- and VIP-induced intestinal fluid secretion through a neural mechanism. The data suggest that NO enhances the release of VIP from nerve terminals and vice versa. Subsequently, each potentiates the other's effect in inducing intestinal fluid secretion.

Animals↗
PubMed1982

Inhibition of Escherichia coli heat-stable enterotoxin effects on intestinal guanylate cyclase and fluid secretion by quinacrine.

Enterotoxigenic Escherichia coli may produce a heat-stable enterotoxin (ST) that causes diarrheal disease in humans and in animals ST activates particulate guanylate cyclase in intestinal mucosal cells and causes intestinal fluid secretion. In this study, we examined the effects of quinacrine on ST activation of guanylate cyclase and ST-mediated intestinal fluid secretion. Quinacrine significantly reduced ST activation of particulate guanylate cyclase in rat intestinal tissue. Additionally, quinacrine reduced ST-mediated fluid secretion in a rat intestinal loop assay (P less than 0.05). In the suckling mouse model, subcutaneous quinacrine (0.1 mumole/mouse) reduced ST-induced fluid secretion at a submaximally effective dose of the toxin, but it did not reduce ST-mediated fluid secretion at a near maximally effective dose. Quinacrine (0.1 mumole/mouse) did not significantly reduce intestinal fluid secretion induced by the analog of cyclic GMP, 8-bromo cyclic GMP. However, at a higher concentration of quinacrine (1 mumole/mouse), significant inhibition of 8-bromo cyclic GMP-induced secretion was observed. Inhibition by the antimalarial agent quinacrine of ST-induced fluid secretion, by a block prior to guanylate cyclase activation, suggests a possible role for a phospholipase early in the sequence of events of ST activation of guanylate cyclase. The results suggest that ST may activate membrane phospholipases prior to ST activation of guanylate cyclase.

Animals↗
PubMed1979

Apolipoprotein A-I synthesis and secretion by cultured human intestinal mucosa.

Cultured human duodenojejunal mucosa was used to study the synthesis and secretion of apoprotein A-I (apoA-I), the major protein constituent of plasma high density lipoproteins. ApoA-I, measured by radioimmunoassay, was secreted continuously into the culture medium over a period of 24 hr. The highest rate was found in the first two hours (34.6 +/- 3.0 ng/mg tissue X hr, mean +/- SE, n = 24). Secretion rate decreased with incubation time, while changes of culture medium increased the rate. ApoA-I secretion was enhanced three- to fourfold by micellar lipid solution and was inhibited by puromycin, ApoA-I synthesis was confirmed by incorporation of 14C-leucine into this apoprotein. The specific activity of apoA-I in medium ultracentrifugal fractions (d less than 1.019 and d = 1.063--1.21 g/ml) was calculated from quantitative data obtained by radioimmunoassay and radioassay of apoA-I separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and found to be about 12 mCi/mmol. These observations indicate that cultured human intestinal mucosa is capable of secreting newly synthesized apoA-I. Organ culture may thus serve as a tool for studying the regulating mechanisms for the synthesis and secretion of this important apoprotein.

Apolipoproteins↗
PubMed1985

Involvement of cyclic AMP and calcium in exocrine protein secretion induced by vasoactive intestinal polypeptide in rat parotid cells.

The effects of vasoactive intestinal polypeptide (VIP) on exocrine protein secretion were studied in enzymatically dispersed cell aggregates from rat parotid glands. VIP (10(-9) - 10(-7) M) stimulated secretion of alpha-amylase in a dose-dependent manner. The VIP-induced release of alpha-amylase was potentiated in the presence of a phosphodiesterase inhibitor. Basal levels of cyclic AMP of the dispersed cells were increased 6.7-fold after stimulation for 10 min by VIP (10(-7) M). The VIP-induced release of alpha-amylase was reduced by 40% when cells were incubated in a Ca2+-free medium in the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). Efflux of 45Ca2+ was significantly increased over basal levels by stimulation with VIP (10(-8) and 10(-7) M), but this increased efflux was approximately only half the increased efflux induced by carbachol (10(-5) M). VIP had no effect on the incorporation of [14C]leucine into protein by parotid cells, whereas incorporation was reduced to 30% of the control value by carbachol (10(-5) M). Thus, the VIP-ergic secretory response in the rat parotid gland is associated with a raised intracellular cyclic AMP level and the mobilisation of a different intracellular Ca2+ pool than that mobilised by carbachol. It is, therefore, closely analogous to the beta-adrenergic response.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Amino acids as possible mediators of the intestinal phase of gastric secretion.

In a group of six dogs with Heidenhain pouches, the infusion of a solution of L-amino acids caused identical increases in gastric secretion when given into the jejunum as when administered directly into the portal venous system. Elevations in plasma amino nitrogen were also similar in the two circumstances. In four dogs with Heidenhain pouches and portacaval transposition, a similar infusion caused an identical increase in gastric secretion when given into the jejunum as when given into the peripheral venous system; plasma amino nitrogen levels were almost as high with the jejunal administration as with venous infusion. It is concluded that all, or almost all, of the gastric secretion evoked by amino acids in the canine intestine can be accounted for by the direct effect of absorbed amino acids on parietal cell secretion, with little or no contribution from release of an intestinal hormone.

Amino Acids↗
PubMed1979

Relation of intestinal metaplasia to the acid-secreting area.

The distribution of intestinal metaplasia in relation to the acid-secreting are was investigated in 66 patients not suffering from gastroduodenal diseases. Studies were made via the endoscopic Congo Red test in combination with the methylene blue staining method. In this test, the acid-secreting area is identified as a "discolored" area in which Congo Red turns from red to blue-black, and areas of intestinal metaplasia were observed as areas staining blue with methylen blue. A close relationship was found between the acid-secreting area and the distribution of intestinal metaplasia; in general, intestinal metaplasia tended to be more extensive and more frequent when the acid-secreting area was small. It was also found that intestinal metaplasia increased with age. However, even in patients who were over 40 years of age, intestinal metaplasia was seen in 12.5% only, if the acid-secreting area was large. Hence, it appears likely that development of intestinal metaplasia is more closely related to the acid-secreting function than to aging.

Adult↗
PubMed1998

Interleukin-6 and small intestinal luminal immunoglobulins.

Our aim was to determine the relationships between interleukin-6 and immunoglobulin levels within small intestinal luminal secretions. Twenty adult subjects with small intestinal bacterial overgrowth (N = 13), irritable bowel syndrome (N = 4), and nonulcer dyspepsia (N = 3) underwent endoscopic aspiration of secretions from the small intestinal mucosal surface for assessment of IL-6, IgA1, IgA2, IgM, IgG1, IgG2, IgG3, and IgG4 concentrations. Serum immunoglobulin concentrations and small intestinal histology were also determined. IgA2 and IgG3 were the predominant IgA and IgG subclasses in luminal secretions in 19/20 (95%) and 20/20 (100%) subjects, respectively. IgA1 and IgG1 predominated in serum in all subjects. No subject had villous atrophy. Luminal IL-6 concentrations correlated significantly with luminal IgA2, IgM, and IgG3 concentrations but not with IgA1 or any other IgG subclass levels. Conversely, luminal IL-6 or immunoglobulin concentrations did not correlate significantly with levels of any immunoglobulin isotype in serum. These observations suggest that important relationships exist between local IL-6 and IgA2, IgM, and IgG3 responses in human small intestinal luminal secretions. Local investigation is mandatory when assessing intestinal immune activity.

Adult↗
PubMed2001

Cooperation of interleukin-17 and interferon-gamma on chemokine secretion in human fetal intestinal epithelial cells.

Interleukin (IL)-17 is a newly identified T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of IL-17 and interferon (IFN)-gamma on chemokine secretion in human fetal intestinal epithelial cells. IL-8 and monocyte chemoattractant protein (MCP)-1 secretion by the human fetal intestinal epithelial cell line, intestine-407, was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analysed by a binding assay using [(125)I]-labelled IL-17. The activation of nuclear factor-kappa B (NF-kappa B), NF-IL6 and AP-1 was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The inducing effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h, and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 and MCP-1 secretion and mRNA abundance. IFN-gamma induced a weak increase in IL-17 R mRNA abundance, and incubation with IFN-gamma for 24 h enhanced [(125)I]-labelled IL-17-binding by 2.4-fold. IL-17 rapidly induced the phosphorylation and degradation of I kappa B alpha molecules, and the combination of IL-17 and IFN-gamma induced a marked increase in NF-kappa B DNA-binding activity as early as 1.5 h after the stimulation. Furthermore, this combination induced an increase in NF-IL-6 and AP-1 DNA-binding activity. In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion by human fetal intestinal epithelial cells. The combination of IL-17 with IFN-gamma synergistically enhanced chemokine secretion. These effects of IL-17 and IFN-gamma might play an important role in the inflammatory responses in the intestinal mucosa.

Cell Line↗
PubMed2002

Interferon-gamma activates EGF receptor and increases TGF-alpha in T84 cells: implications for chloride secretion.

IFN-gamma inhibits intestinal Cl(-) secretion, in part via downregulation of CFTR and Na(+)-K(+)-ATPase activity and expression, but the proximal signaling events were unknown. We have shown that transforming growth factor-alpha (TGF-alpha) inhibits calcium-activated Cl(-) secretion, and effects of IFN-gamma in other systems are mediated via EGF family members. We tested whether IFN-gamma inhibits Cl(-) secretion via EGF receptor (EGFr) activation. IFN-gamma increased tyrosine phosphorylation in T84 cells at 24 h, including the EGFr. IFN-gamma also increased cell-associated pro-TGF-alpha, as well as free TGF-alpha in the bathing media. However, whereas IFN-gamma significantly inhibited carbachol-induced Cl(-) secretion, neither neutralizing antibodies to TGF-alpha nor an EGFr inhibitor (1 microM tyrphostin AG 1478) were able to reverse this inhibitory effect. AG 1478 also failed to reverse IFN-gamma-induced tyrosine phosphorylation of the EGFr, but receptor phosphorylation was attenuated by both the neutralizing antibody to TGF-alpha and PP2, a Src kinase inhibitor. Moreover, PP2 reversed the inhibitory effect of IFN-gamma on Cl(-) secretion. In total, our findings suggest an increase in functional TGF-alpha and activation of the EGFr in response to IFN-gamma. The release of TGF-alpha and intracellular Src activation likely combine to mediate EGFr phosphorylation, but only Src appears to contribute to the inhibition of transport. Nevertheless, because TGF-alpha plays a role in restitution and repair of the intestinal epithelium after injury, we speculate that these findings reflect a feedback loop whereby IFN-gamma modulates the extent of cytokine-induced intestinal damage.

Antibodies↗