Cutting edge: peripheral neuropeptides attract immature and arrest mature blood-derived dendritic cells. (41/608)

Dendritic cells (DC) are highly motile and play a key role in mediating immune responses in various tissues and lymphatic organs. We investigated locomotion of mononuclear cell-derived DC at different maturation stages toward gradients of sensory neuropeptides in vitro. Calcitonin gene-related peptide, vasoactive intestinal polypeptide, secretin, and secretoneurin induced immature DC chemotaxis comparable to the potency of RANTES, whereas substance P and macrophage-inflammatory protein-3beta stimulated immature cell migration only slightly. Checkerboard analyses revealed a true chemotactic response induced by neuropeptides. Upon maturation of DC, neuropeptides inhibited spontaneous, macrophage-inflammatory protein-3beta- and 6Ckine-induced cell migration. Maturation-dependent changes in migratory behavior coincided with distinct neuropeptide-induced signal transduction in DC. Peripheral neuropeptides might guide immature DC to peripheral nerve fibers where high concentrations of these peptides can arrest the meanwhile matured cells. It seems that one function of sensory nerves is to fasten DC at sites of inflammation.  (+info)

Isolation of functional polarized bile duct units from mouse liver. (42/608)

The development of genetically altered murine animals has generated a need for in vitro systems in the mouse. We have now characterized a novel isolated bile duct unit (IBDU) preparation from the mouse to facilitate such studies. The mouse IBDU is isolated by portal perfusion of collagenase, blunt dissection, further enzymatic digestions, filtering through sized mesh, and culturing on Matrigel for 16-72 h. This mouse IBDU forms a central, enclosed lumen lined by polarized cytokeratin-19-positive cholangiocytes with numerous microvilli on the apical membrane. The IBDU responds to secretory stimuli, including secretin, vasoactive intestinal peptide, IBMX, and forskolin, resulting in expansion of the central lumen from secretion as quantified by videomicroscopy. The secretory response to secretin is dependent on Cl- and HCO3-in the perfusate. These findings indicate that mouse IBDUs are intact, polarized, functional bile duct secretory units that permit quantitative measurements of fluid secretion from mouse bile duct epithelium for the first time. This method should facilitate studies of cholangiocyte secretion in genetically altered murine animal models.  (+info)

Roles of 5-HT receptors in the release and action of secretin on pancreatic secretion in rats. (43/608)

5-Hydroxytryptamine (serotonin, 5-HT) is a hormone and neurotransmitter regulating gastrointestinal functions. 5-HT receptors are widely distributed in gastrointestinal mucosa and the enteric nervous system. Duodenal acidification stimulates not only the release of both 5-HT and secretin but also pancreatic exocrine secretion. We investigated the effect of 5-HT receptor antagonists on the release of secretin and pancreatic secretion of water and bicarbonate induced by duodenal acidification in anesthetized rats. Both the 5-HT(2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron at 1-100 microg/kg dose-dependently inhibited acid-induced increases in plasma secretin concentration and pancreatic exocrine secretion. Neither the 5-HT(1) receptor antagonists pindolol and 5-HTP-DP nor the 5-HT(4) receptor antagonist SDZ-205,557 affected acid-evoked release of secretin or pancreatic secretion. None of the 5-HT receptor antagonists affected basal pancreatic secretion or plasma secretin concentration. Ketanserin or ondansetron at 10 microg/kg or a combination of both suppressed the pancreatic secretion in response to intravenous secretin at 2.5 and 5 pmol x kg(-1) x h(-1) by 55-75%, but not at 10 pmol x kg(-1) x h(-1). Atropine (50 microg/kg) significantly attenuated the inhibitory effect of ketanserin on pancreatic secretion but not on the release of secretin. These observations suggest that 5-HT(2) and 5-HT(3) receptors mediate duodenal acidification-induced release of secretin and pancreatic secretion of fluid and bicarbonate. Also, regulation of pancreatic exocrine secretion through 5-HT(2) receptors may involve a cholinergic pathway in the rat.  (+info)

MEK inhibits secretin release and pancreatic secretion: roles of secretin-releasing peptide and somatostatin. (44/608)

We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with pancreatobiliary cannulas and isolated upper small intestinal loops were perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were diverted. The effect of intravenous MEK on acid-stimulated secretin release and pancreatic exocrine secretion was then studied with or without coinfusion of naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid perfusate, which contains secretin-releasing peptide (SRP) activity, was collected from donor rats with or without pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused intraduodenally into recipient rats. MEK increased plasma SS concentration and inhibited secretin release and pancreatic fluid and bicarbonate secretion dose-dependently. The inhibition was partially reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from MEK-treated donor rats; this was partially reversed by coinfusion with naloxone or anti-SS serum. These results suggest that in the rat, MEK inhibition of acid-stimulated pancreatic secretion and secretin release involves suppression of SRP activity release. Thus the MEK inhibitory effect appears to be mediated in part by endogenous SS.  (+info)

Neonatal secretion of secretin. (45/608)

The plasma levels of secretin have been measured in mothers after labour, and in their babies at birth and on day 4 of life. The mean cord venous level was higher than the maternal level, and there was a significant correlation between the individual maternal and cord values. The level had again increased by day 4, and at this time the secretin level was inversely proportional to the blood glucose level.  (+info)

A randomized controlled crossover study comparing synthetic porcine and human secretins with biologically derived porcine secretin to diagnose Zollinger-Ellison Syndrome. (46/608)

BACKGROUND: Although biologically-derived porcine secretin is approved for the diagnosis of Zollinger-Ellison Syndrome, it is no longer available in the United States. Pure human and porcine secretins have now been synthesized and new drug applications have been filed with the Federal Drug Administration (FDA). METHODS: In the current study we compared secretin testing results in six confirmed Zollinger-Ellison Syndrome patients using the biologically-derived product and both synthetic products (human and porcine) in a three-way, randomized, single-blind Latin-squares crossover study. RESULTS: Using the FDA-approved criterion for positive secretin testing (i.e. a serum gastrin concentration increase of > 110 pg/mL), there was complete agreement between all three agents for all patients. With the more stringent NIH criterion (i.e. a serum gastrin concentration increase of > 200 pg/mL), positive results persisted in five out of six, six out of six and four out of six patients using biologically-derived secretin, synthetic porcine secretin, and synthetic human secretin, respectively (six out of six, six out of six and four out of six if a positive test was defined as a 50% increase in serum gastrin concentration). The time to peak serum gastrin concentration after secretin injection occurred within 15 min in all studies (in 94% by 10 min and in 77% by 5 min). Three-way comparisons of serum gastrin concentrations showed a single statistically significant difference (the change from baseline at 15 min between synthetic human and synthetic porcine secretin, P=0.0274). Statistically significant changes from baseline occurred at 1, 2 and 5 min for biologically-derived porcine secretin and at 2 and 5 min for both synthetic porcine and synthetic human secretin, in keeping with the expected time curve for positive tests. All three agents were well-tolerated. CONCLUSIONS: These data suggest that either synthetic secretin product, when released onto the United States market, can be used to confirm Zollinger-Ellison Syndrome.  (+info)

Comparison of the actions of porcine secretin and extracts of chicken duodenum on pancreatic exocrine secretion in the cat and turkey. (47/608)

1. Extracts were prepared of chicken duodenum and their actions on pancreatic secretion in urethane anasthetized turkeys and in conscious cats were compared with those of pure natural porcine secretin. 2. The chicken extracts and porcine secretin stimulated dose-dependent increases in the rate of flow, but not the rate of protein secretion, from the pancreas in cats and turkeys. 3. Porcine cholecystokinin stimulated both the rate of flow and the rate of protein secretion from the pancrease in turkeys. 4. The doses of chicken extract required to evoke half maximal rates of flow of pancreatic juice were similar in the turkey (0-55 mg/kg) and in the cat (0-72 mg/kg). The highest concentration of bicarbonate recorded in the turkey responses was 30 m-equiv/l. compared with 112 m-equiv/l. in the cat. 5. The dose of porcine secretin required for half maximal rate of flow in the bird (5-9 mug/kg) was 180 times higher than in the mammal (0-33 mug/kg). In the cat the duration of responses to porcine secretin was significantly greater than to the chicken extract. 6. It is concluded that in birds there is a factor with biological properties similar but not identical to those of porcine secretin, and that this factor may regulate pancreatic secretion by a mechanism resembling the secretin mechanism in mammals.  (+info)

Effect of metiamide on the response to secretin and cholecystokinin in man. (48/608)

The effects of intravenous metiamide on the pancreatic exocrine response to intravenous infusion of secretin plus cholecystokinin has been studied in eight patients with duodenal ulceration. The secretion of bicarbonate and water was not altered by metiamide. The secretion of enzymes was significantly less than control during infusion of metiamide. The differences between the pancreatic and gastric responses to metiamide are discussed.  (+info)