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R Nustede

Publications and source records attributed to R Nustede.

At least 37 records · Page 2Linked to original sources
PubMed1994

Gastrin-releasing peptide and CCK after intraduodenal inhibition of proteases in dogs.

The intraduodenal application of a potent protease inhibitor (camostate, 600 mg) causes a significant increase in basal pancreatic secretion in the manner of a negative-feedback mechanism. The integrated protein secretion during the entire study period was 9.9 +/- 1.8 g in 120 min. The iv application of anti-GRP immunoglobulin caused a significant reduction to 5.0 +/- g in 120 min. No significant changes in the plasma concentrations of GRP and CCK were detectable. The increased secretion occurring after the administration of the protease inhibitor could be mediated by neural GRP-dependent mechanisms. These may also be relevant for CCK-dependent factors, which are only briefly mentioned.

Animals↗
PubMed1994

Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans.

BACKGROUND/AIMS: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. METHODS: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol.kg-1.h-1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol.kg-1.h-1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. RESULTS: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol.kg-1.h-1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. CONCLUSIONS: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antral and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.

Adult↗
PubMed1994

Identification and biochemical characterization of the human brain galanin receptor.

Human galanin (hGal) is an important neuro-modulator present in the brain, gastrointestinal system and the hypothalamo-pituitary axis. A specific receptor for hGal has been identified in various areas in human brain. A single class of high affinity binding sites was found on plasma membranes of the amygdala (Kd 0.23 nM, Bmax 44 fmol/mg), the hypothalamus (Kd 0.20 nM, Bmax 25 fmol/mg) and the cortex cerebri (Kd 0.11 nM, Bmax 8.2 fmol/mg). Other brain areas, i.e. cerebellum, thalamus or pons, expressed binding sites of identical high affinity in lower quantities (Bmax < 3 fmol/mg). Specific binding of 125I-labelled hGal was found to be reversible, time- and temperature-dependent and inhibited by Ca2+, Na+ and K+ ions at a concentration of 5 mM. Non-hydrolysable guanosine nucleotides potently reduced specific binding of 125-I-labelled hGal by more than 80%. Synthetic hGal analogues substituted in the N-terminal region exhibited strongly reduced binding affinity for the hGal receptor. Using 3-[(3-cholamidopropyl) dimethylammonio]-2-hydroxy-1-propanesulphonate, hGal receptors were successfully solubilized from human cortical membranes, exhibiting no significant loss of binding affinity. Affinity cross-linking to 125I-labelled hGal revealed a labelled band of approximately 60 kDa sensitive to unlabelled Gal. This putative hGal receptor is glycosylated since its molecular size was reduced after treatment with endoglycosidase F. Receptors bound to 125I-labelled hGal could be specifically adsorbed to wheat germ agglutinin and ricinus communis agglutinin, suggesting that receptor glycosylation involves N-acetyl glucosamine and galactose respectively.

Agglutinins↗
PubMed1993

Role of neurotensin in the regulation of exocrine pancreatic secretion in dogs.

A potential physiological function of the regulatory gastrointestinal peptide neurotensin (NT) is the stimulation of exocrine pancreatic secretion. We investigated therefore whether immunoneutralization of the postprandially circulating peptide, intravenous application of either atropine or the highly specific CCK receptor antagonist, L-364,718, could influence neurotensin-mediated pancreatic secretion in dogs. The use of CCK receptor antagonist (0.1 mg kg-1 intraduodenally) inhibited postprandial and NT-mediated exocrine pancreatic secretion. The integrated postprandial protein secretion fell from 31 +/- 1.6 to 23 +/- 2.1 g 180 min-1 while the corresponding values in response to i.v.-NT (postprandial neurotensin concentration course was imitated by the infusion of 50 pmol kg h-1 NT) fell from 22 +/- 1.9 to 7.5 +/- 0.8 g 180 min-1. Immunoneutralization of postprandial NT led to a simultaneous significant reduction in postprandial pancreatic secretion (integrated protein release 31 +/- 1.6 and 15.5 +/- 1.4 g 180 min-1 respectively). The i.v. application of atropine lowered NT-mediated pancreatic secretion (e.g., protein output) from 22 +/- 1.9 to 7.1 +/- 7.1 +/- 0.9 g 180 min-1. We conclude that NT plays an important role in the endocrine regulation of exocrine pancreatic secretion. This influence could be mediated by a CCK-dependent cholinergic mechanism.

Animals↗
PubMed1993

[Metabolic parameters and neurotensin liberation after resection of the small intestine, syngeneic and allogeneic segment transplantation the rat].

The aim of the following study was to gain some insight into the functional characteristics of different portions of the small intestine after either partial resection or syngeneic and allogeneic transplantation 3 months postoperatively. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small-bowel resection (n = 21), syngeneic (Lewis-->Lewis, n = 21), or allogeneic transplantation (Brown Norway-->Lewis, n = 24). The length of the remnant, isograft, or allograft was 27 cm (i.e., one-third of the rat small intestine) and consisted of the proximal (n = 7), middle (n = 7), or distal (n = 7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation cyclosporine (15 mg/kg body wt. s.c.) was administered for graft acceptance. The control group was not operated upon, but was composed of weight- and age-matched Lewis rats (n = 7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all three portions investigated (P < 0.01), but did not affect maltose absorption. Excretion of fecal fat was elevated significantly only after distal resection (P < 0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P < 0.05) in all three different intestinal grafts. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The role of pancreatic innervation and cholecystokinin in the intestinal phase of pancreatic polypeptide release in conscious dogs.

Besides vagal cholinergic mechanisms, pancreatic polypeptide (PP) secretion is thought to be mediated by hormones. This study was performed to delineate the role of extrinsic pancreatic innervation and cholecystokinin (CCK) in amino acid- and fat-stimulated PP secretion. In ten mongrel dogs, pancreatic denervation was performed by the method of Debas et al. [3]. Total denervation of the pancreas did not alter PP response to intraduodenal application of amino acids (integrated output 24,434 +/- 3260 pmol/1 x 120 min before vs 22,797 +/- 2470 pmol/1 x 120 min after operation) and to intraduodenal fat solution (19,595 +/- 2121 pmol/1 x 120 min vs 19,983 +/- 2031 pmol/1 x 120 min). Also, no significant differences were measured in CCK release (491 +/- 71 pmol/1 x 120 min vs 430 +/- 57 pmol/1 x 120 min for amino acids, 571 = 63 pmol/1 x 120 min vs 563 +/- 89 pmol/1 x 120 min for fat solution). Plasma PP and CCK levels were compared by linear regression analysis. Correlations between PP and CCK were high in the intact pancreas (amino acids, r = 0.92; fat, r = 0.99) as well as in the denervated pancreas (r = 0.93 amino acids and r = 0.98 fat). These results show that extrinsic pancreatic innervation does not influence PP and CCK release after intraduodenal amino acids or fat solution and that PP secretion seems to be mediated to some extent through the release of CCK.

Amino Acids↗
PubMed1993

The adaptive response of the rat small intestine after resection and segmental transplantation during the early postoperative phase.

Organ harvesting from a living donor or spatial constraints in the recipient's abdominal cavity are the main factors to be considered in the segmental transplantation of the small intestine. It was the aim of the following study to gain insight into the functional characteristics of different portions of the small intestine either after partial resection or syngeneic and allogeneic transplantation during the early postoperative period. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small bowel resection (n = 21), syngeneic (Lewis-->Lewis, n = 21), or allogeneic transplantation (Brown Norway-->Lewis, n = 24). The length of the remnant, isograft, or allograft was 27 cm (i.e. one third of the rat small intestine) and consisted of the proximal (n = 7), middle (n = 7), or distal (n = 7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation, cyclosporine (15 mg/kg BW s.c.) was administered for graft acceptance. Controls were unoperated, weight- and age-matched Lewis rats (n = 7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all the three portions investigated (P < 0.01) but did not affect maltose absorption. Excretion of fecal fat was elevated after distal resection (P < 0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P < 0.05) in all three different intestinal grafts. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation. Postmortem examination revealed no signs of acute rejection. When transplantation of short intestinal segments is considered, it is of vital importance to take into account the functional differences and the influence of immunosuppressive drug therapy in the regulatory bowel function.

Adaptation, Physiological↗
PubMed1993

Fat-stimulated cholecystokinin release following transplantation of the entire small bowel or of different intestinal segments in rats.

This study presents data on the fat-stimulated release of cholecystokinin (CCK) in conscious rats 11 and 84 days after one-stage transplantation of the entire small bowel, or of jejunal, jejunoileal, or ileal segments, under syngeneic and allogenic conditions. After allotransplantation, ciclosporin (CsA) was administered for graft acceptance. The results were compared with those in unoperated controls and in animals that had undergone small-bowel resections leaving jejunal, jejunoileal, or ileal remnants. When the entire small bowel was grafted under syngeneic (92.5 +/- 8.3; 106.6 +/- 7.5) or allogeneic (110.5 +/- 5.5; 101.2 +/- 6.9) conditions, CCK release (pg/ml per 60 min) was similar (P > 0.05) to that of the controls (110.3 +/- 9.0; 94.7 +/- 6.8) at both measurement points. Recipients of jejunal or ileal segmental isografts showed a significantly elevated (P < 0.05) output of CCK (jejunal graft: 176.4 +/- 18.5; 125.5 +/- 10.1 -ileal graft: 55.9 +/- 9.0; 30.1 +/- 5.4) compared with corresponding small-bowel resections (jejunal remnant: 69.0 +/- 7.9; 93.5 +/- 3.9-ileal remnant: 16.7 +/- 3.7; 6.6 +/- 1.3). In contrast, the difference was not significant (P > 0.05) when jejunoileal segments were grafted (jejunoileal graft: 74.4 +/- 19.6; 47.0 +/- 10.4-jejunoileal remnant: 50.7 +/- 11.0; 47.0 +/- 11.9). All recipients of jejunal allografts died between day 8 and day 10 after transplantation, due to functional impairment. Two-stage segmental jejunal allotransplantation, with insertion of the graft into the continuation of the gastrointestinal tract in an accessory, non-functional position after 28 days was successful. Due to this technique, we could gather data on day 84. Recipients of jejunal (118.2 +/- 7.6), jejunoileal (87.1 +/- 19.7; 48.6 +/- 9.3), or ileal (48.1 +/- 6.7; 21.6 +/- 4.6) allografts showed no significant (P < 0.05) differences in CCK output compared with isografts, either on day 11 or on day 84. Our data indicate that transplantation of the entire small bowel affects the fat-stimulated CCK release neither in the early postoperative period nor 3 months after transplantation. In contrast, transplantation of jejunal or ileal segmental isografts caused a significantly elevated output of CCK compared with corresponding resection remnants. Immunosuppression with CsA did not affect CCK release after transplantation, but led to functional impairment with fatal outcome when a short jejunal segment was grafted. This could be prevented by applying the two-stage technique.

Animals↗
PubMed1993

The influence of bile acids on the regulation of exocrine pancreatic secretion and on the plasma concentrations of neurotensin and CCK in dogs.

The influence of the intestinal bile acid content on the secretion of the exocrine pancreas and on the plasma concentrations of the relevant peptides (NT), and CCK is the subject of continuing controversy. Thus the alterations of pancreatic secretion and both hormones during variations of intestinal bile acid content were investigated. Modified Herrera fistulas were implanted in six dogs for analysis of the pancreatic secretions. Intraduodenal application of taurocholate (1.8, 3.6, or 7.2 mM) led to a marked reduction of the pancreatic secretion as well as to a simultaneous decrease of NT and CCK release after stimulation by the intraduodenal instillation of a 20% lipid emulsion. (The integrated protein secretion decreased from 20.1 +/- 1.9 g to 15.2 +/- 1.6 g, NT release dropped from 4970 to 3050 pg/180 min, and CCK from min.) cholestyramine together with the lipid emulsion had the opposite effect. The pancreatic protein as well as NT and CCK release increased. It therefore appears that there is a negative feedback relationship between the postprandial intestinal bile acid content on the one hand, and the secretion of the exocrine pancreas and the regulatory peptides NT and CCK on the other hand. This relationship is independent of any interaction between pancreatic proteases and bile acids.

Animals↗
PubMed1993

Partial hepatectomy affects pancreatic size and function in rats.

The effect of partial hepatectomy (62 +/- 2% of liver mass) or sham laparotomy on the pancreas was studied in rats. Pancreatic contents of DNA, protein, and digestive enzymes were measured 14 days postoperatively. Pancreatic acini were prepared to study exocrine pancreatic function after hormonal stimulation. Islet hormone release was investigated in the isolated perfused pancreas. Liver regeneration reached 93 +/- 1% within 14 days. Water contents in liver and pancreas remained unaltered. Simultaneously, the pancreatic weight increased significantly. Pancreatic enzymes showed a parallel elevation, whereas DNA remained unaffected. Amylase secretion from pancreatic acini was unaltered. Stimulated insulin and somatostatin release from the perfused pancreas were both increased. Plasma cholecystokinin levels were elevated, whereas neurotensin was decreased. Insulin and gastrin remained unchanged. In conclusion, after partial hepatectomy, enhanced cholecystokinin and decreased neurotensin blood levels are suggested to contribute to a hypertrophic effect on the exocrine pancreas and an adaptive regulation of the endocrine gland.

Amylases↗
PubMed1993

Feedback regulation of exocrine pancreatic secretion in dogs.

Important basic physiological mechanisms of exocrine pancreas secretion were delineated in a canine model. However, dogs have been considered unsuitable for the study of the controversial feedback regulation of exocrine pancreas secretion. The present study reveals a marked modification of pancreas secretion following the intraduodenal instillation of lipase: The postprandial lipase secretion decreases from 2,421 U x 180 min-1 to 1,490 U x 180 min-1, but simultaneously determined cholecystokinin (CCK) concentrations in plasma do not increase under these circumstances. The intraduodenal application of a protease inhibitor (800 mg camostate) significantly stimulates the secretion of the exocrine pancreas in the fasting dog: After 15 min the protein release increased to 133 +/- 30 mg. Intravenous atropine blocks this increase. The plasma concentrations of CCK are not significantly influenced. These results in our canine model show that the secretory activity of the exocrine pancreas depends on the intraduodenal enzyme content. CCK is irrelevant in this context.

Animals↗
PubMed1993

Gastrin-releasing peptide and cholecystokinin in the regulation of exocrine pancreatic secretion in dogs.

Exocrine pancreatic secretion in conscious dogs is significantly stimulated by the intravenous application of small doses of gastrin-releasing peptide (GRP; 30 pmol x kg-1 x h-1). There is no increase of the GRP concentrations in peripheral blood which is also the case under physiological postprandial conditions. There is also no increase in the peripheral cholecystokinin (CCK) concentrations, in contrast to previous reports. Nevertheless other CCK-related mechanisms may play an important role, since the administration of the highly specific CCK receptor antagonist MK-329 causes a marked reduction of the GRP-induced exocrine pancreatic secretion.

Animals↗
PubMed1992

Determination of plasma cholecystokinin (CCK) concentrations by bioassay and radioimmunoassay in man. A critical evaluation.

The present investigation was designed to perform a direct comparison of a rat pancreatic acini bioassay system and a specific CCK radioimmunoassay (antiserum G-160) for the measurement of fasting and meal-stimulated plasma CCK in the presence and absence of the CCK receptor antagonist loxiglumide. The G-160 CCK antiserum is directed against the C-terminal O-sulfated tyrosine residue of the CCK molecule which is essential for full bioactivity of CCK peptides. For plasma extraction prior to bioassay measurement, hydrophobic reverse-phase chromatography on octadecylsilane cartridges was employed and resulted in simultaneous adsorption and elution of both CCK peptides and loxiglumide with recoveries of 87.5 +/- 9% and 75.0 +/- 5.9%, respectively. In the absence of loxiglumide, fasting and meal-stimulated values for CCK-like bioactivity and CCK-immunoreactivity (IR-CCK) were nearly identical (basal values: 1-2 pmol/l; meal-stimulated plateau levels: 4-6 pmol/l). After intravenous infusion of loxiglumide (30 mg/kg/h for 10 min, 10 mg/kg/h thereafter), resulting in plasma steady state levels of 200-300 mumol/l, meal-stimulated CCK-like bioactivity was undetectable, whereas IR-CCK levels were augmented 6.5-fold. In the bioassay system, standard samples containing 50 mumol/l loxiglumide produced complete inhibition of acinar lipase release in response to 50 pmol/l synthetic CCK-8. We conclude, that postprandial circulating non-CCK-like factors do not contribute significantly to the direct receptor-mediated stimulation of exocrine pancreatic secretion. The good agreement of CCK-like bioactivity and IR-CCK levels in the absence of loxiglumide confirms the sensitive and specific recognition of bioactive CCK peptides by the G-160 antiserum and suggests that this antibody exerts binding characteristics probably similar to a pancreatic acinar receptor.

Adult↗