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Biomedical subjects

K H Herzig

Publications and source records attributed to K H Herzig.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of fecal elastase-1 determination with the secretin-cholecystokinin test in patients with cystic fibrosis.

BACKGROUND: The secretin-cholecystokinin (CCK) test is the gold standard in the evaluation of exocrine pancreatic insufficiency. Because of its invasive character, it is of limited value in cystic fibrosis (CF) patients, especially in those with severe respiratory disease. The aim of the study was to evaluate the sensitivity of fecal elastase-1 in relation to the secretin-CCK test and quantitative fecal fat excretion in CF patients. METHODS: The study comprised 28 patients (11 females and 17 males) aged 4 to 20 years. In all patients the secretin-CCK test and determination of fecal elastase-1 concentration (with enzyme-linked immunosorbent assay) and fecal fat excretion were performed. RESULTS: The range of fecal elastase-1 was from undetectable to 485 microg/g (mean, 84.6+/-119.9 microg/g) and of fecal fat excretion from 1.0 to 55.1 g/day (mean, 15.0+/-12.2 g/day). On the basis of the results of the secretin-CCK test (and fecal fat analysis) exocrine pancreatic insufficiency was divided into three subgroups: mild (I), moderate (II), and severe (III). Four patients were classified in subgroup I, 4 in II and 20 in III. Fecal elastase (elastase-1) results were 332.0+/-124.9 microg/g in subgroup I, 96.9+/-45.7 microg/g in subgroup II, and 32.1+/-41.2 microg/g in subgroup III. The fecal elastase-1 sensitivity with a cut-off point of 200 microg/g was 89.3% for all patients, 100% for patients in subgroups II and III, but only 25.0% for patients in subgroup I; the specificity was 96.4%. Linear regression analysis showed a statistically significant correlation between fecal elastase (elastase-1) and duodenal volume, bicarbonate, amylase, lipase, and trypsin secretion (in all cases P < 0.001). CONCLUSIONS: Measurement of fecal elastase-1 is simple and very useful for assessing the exocrine pancreatic function in CF patients. Elastase is highly specific in severe and moderate exocrine pancreatic insufficiency, but it is rather unspecific for milder forms of pancreatic insufficiency.

Adolescent↗
PubMed1998

Expression of functional GABAA receptors in cholecystokinin-secreting gut neuroendocrine murine STC-1 cells.

1. Gastrointestinal neuroendocrine (NE) cells synthesize, store and secrete gamma-aminobutyric acid (GABA). Recently, an autocrine-paracrine function of GABA has been proposed for secretion from NE cells. 2. To search for functional GABAA receptors in NE gut cells, we performed whole-cell and perforated-patch-clamp studies in the intestinal cholecystokinin (CCK)-secreting NE cell line STC-1. 3. Application of GABA evoked currents in STC-1 cells. These effects were mimicked by muscimol, an agonist of GABAA receptors, and blocked by picrotoxin or bicuculline, antagonists of GABAA receptors. The GABA- or muscimol-activated currents reversed near 0 mV, which under the recording conditions used was consistent with the activation of the GABAA receptor-Cl- channel complex. 4. In contrast to the effect on most neurons, GABA as well as muscimol led to a (reversible) depolarization of the membrane potential of STC-1 cells. Membrane depolarization in turn activated voltage-gated Ca2+ channels and increased intracellular Ca2+ concentrations in STC-1 cells. 5. In accordance with the observed membrane depolarization and activation of voltage-gated Ca2+ channels, both GABA and muscimol stimulated Ca2+-dependent CCK release. In contrast, bicuculline inhibited the GABA-induced secretion of CCK. 6. Using the reverse transcription-polymerase chain reaction (RT-PCR), mRNA of the GABAA receptor subunits alpha2, alpha3, alpha5, beta1, beta3 and delta could be detected in STC-1 cells. 7. In summary, we have shown that the CCK-secreting gut NE cell line STC-1 expresses functional GABAA receptors and that GABA stimulates CCK release. Thus, GABA is involved in the fine tuning of CCK secretion from the gut NE cell line STC-1.

Animals↗
PubMed1998

Regulation of the action of the novel cholecystokinin-releasing peptide diazepam binding inhibitor by inhibitory hormones and taurocholate.

Diazepam binding inhibitor (DBI1-86) has recently been isolated in search for a cholecystokinin (CCK)-releasing peptide in the duodenum that is responsible for the feedback regulation of exocrine pancreatic secretion. Synthetic porcine DBI1-86 stimulates CCK release in vivo and in vitro from isolated intestinal mucosal cells. We postulated that DBI intraduodenally releases CCK in a paracrine fashion and might be the missing link in the feedback regulation of exocrine pancreatic secretion. Somatostatin, peptide YY (PYY) and taurocholate are known to inhibit feedback-stimulated CCK release in the rat. In this study, we investigated the effect of somatostatin, PYY and taurocholate on DBI-stimulated CCK secretion. Dispersed rat intestinal mucosal cells were prepared from the proximal small bowel and continuously perfused. The perfusate was collected and the release of CCK into the medium was measured. DBI1-86 dose-dependently stimulated CCK release, with a maximal effect at 10(-9) M. Somatostatin blocked the DBI-stimulated CCK release. Pretreatment of the cells with pertussis toxin fully reversed the inhibitory effect of somatostatin on DBI-stimulated CCK secretion, suggesting that somatostatin exerts its action by an inhibitory G-protein. In contrast, PYY (10(-6) M) and taurocholate (10(-6) M) did not affect DBI stimulated CCK levels, indicating that they act through different mechanisms to inhibit feedback-stimulated CCK release.

Animals↗
PubMed1998

Cholecystokinin- and secretin-releasing peptides in the intestine--a new regulatory interendocrine mechanism in the gastrointestinal tract.

Maintenance of homeostasis in the upper small bowel is a vital process for the body and therefore highly controlled. The enteric nervous system and the endocrine system are the regulators in this process influencing each other. The endocrine system in the gut consists of the classical hormones [cholecystokinin (CCK) secretin] to evoke motility or secretion. They are under control of releasing factors which are probably influenced by the enteric nervous system. Diazepam binding inhibitor and luminal CCK-releasing factor are likely candidates for CCK-releasing peptides in the negative feedback process in the absence of pancreatic juice. Experimental evidence suggests a secretin-releasing peptide. Further studies will be needed to determine the physiological role of each of these peptides. Monitor peptide in the pancreatic juice seems to function as a specific positive enhancement for CCK release. All these peptides are inactivated by the proteolytic enzymes during the interdigestive period. The discovery of additional releasing peptides and factors is very likely.

Amino Acid Sequence↗
PubMed1998

Evaluation of a cacao drink as a simple oral stimulus to assess gallbladder contraction.

UNLABELLED: Gallbladder contractility plays an important role in the pathogenesis of gallstones and in the course of cholelithiasis. Furthermore, a functioning gallbladder is an important condition for performing a successful disolution of gallstones by bile acids. Therefore, a reliable simple physiological test is desired to assess gallbladder contractility. In ten volunteers gallbladder contraction was stimulated by 50 g chocolate, 330 ml cacao drink or in comparison by intramuscular injection of 0.3 microgram/kg ceruletide. Gallbladder volume was measured sonographically and CCK in serum was determined by radioimmunoassay (RIA) after 0, 15, 30 and 45 min. Additionally gallbladder contraction was determined in 20 patients with symptomatic gallstones using cacao drink on ceruletide. In health volunteers remaining gallbladder volume after 30 min was 28% +/- 5% using ceruletide and 37% +/- 7% using cacao. Stimulation by chocolate resulted in a remaining volume of 59% +/- 12% after 45 min only. Simultaneously to gallbladder contraction an increase of CCK in serum was registered. 30 min after cacao CCK had increased from 0.9 to 3.3 pmol/l. Using chocolate an increase of CCK amounted to 2.1 pmol/l after 45 min only. In patients with gallstones the positive predictive value of the cacao test for a functioning gallbladder was 91% and the negative predictive value was 78% in comparison to the unphysiologic stimulation by ceruletide injection. CONCLUSION: Cacao test but not chocolate is suitable and reliable to assess gallbladder contraction in patients with symptomatic gallstones.

Adult↗
PubMed1997

c-met expression in pancreatic cancer and effects of hepatocyte growth factor on pancreatic cancer cell growth.

Hepatocyte growth factor (HGF) is a widely expressed growth factor secreted by cells of mesenchymal origin, which has been shown to be involved in growth processes of multiple cell types. The HGF receptor, the product of the c-met protooncogene, is expressed mainly by epithelial cells. Increased expression of the HGF receptor has been observed in various tumors. To investigate the expression of the HGF receptor in the pancreas, we analyzed rat and human normal tissue and pancreatic carcinoma by Western blot analysis. We observed weak expression of c-met reactivity in normal pancreas but markedly enhanced expression in both rat and human pancreatic cancer. To test the possibility that HGF could act as a growth factor on pancreatic carcinoma, the effects of HGF on DNA synthesis in a rat and two human pancreatic carcinoma cell lines were analyzed. HGF induced dose-dependent [3H]thymidine incorporation, reaching 320, 210, and 180% above unstimulated controls in AR4-2J, PancTu-1, and 818/4 cells, respectively. The activation of signal transduction pathways by HGF was further analyzed in AR4-2J cells. After stimulation, a rapid and intense increase in receptor tyrosine phosphorylation was detected. Furthermore, HGF induced a time- and dose-dependent induction of c-fos expression. The addition of tyrphostin, a specific tyrosine kinase inhibitor, prevented c-fos induction and inhibited HGF-induced [3H]thymidine incorporation. In summary, our results demonstrate strongly increased HGF receptor expression in pancreatic carcinoma and support the assumption that HGF could act as a growth promoting factor on this cancer via stimulation of tyrosine kinases.

Animals↗
PubMed1997

Red kidney bean lectin is a potent cholecystokinin releasing stimulus in the rat inducing pancreatic growth.

BACKGROUND: Lectins are proteins capable of specific binding to carbohydrates without altering their covalent structure. As an essential part of plants they are ingested in our daily diet. By binding to glycosyl side chains of receptors lectins can mimic or inhibit the action of the ligand. Oral administration of phytohaemagglutinin (PHA) in rats dose dependently induces growth of the small intestine and the pancreas by an unknown mechanism. AIMS: To investigate the mechanism of PHA induced intestinal and pancreatic growth. METHODS: Thirty day old male rats were pairfed for 10 days with lactalbumin as a control diet or lactalbumin plus PHA or purified soybean trypsin inhibitor (STI) as a positive control (42 mg/rat/day) with or without 20 micrograms of the cholecystokinin A (CCK-A) antagonist MK 329. To investigate further the effect of PHA on CCK release intestinal mucosal cells were isolated from rats which were continuously perfused in a perfusion apparatus. CCK release into the medium was assayed. RESULTS: PHA and STI significantly stimulated growth of the pancreas and the small intestine. MK 329 blocked this growth effect in the pancreas but not in the small intestine. In vivo, PHA significantly increased CCK plasma levels from 0.75 to 6.67 (SEM 2.23) compared with 2.3 (0.35) pM in the control group. In addition, in vitro PHA dose dependently stimulated CCK release with a maximal effect at 100 ng/ml. CONCLUSION: In vivo and in vitro PHA is a potent stimulus for CCK release in the rat, thereby inducing pancreatic growth, whereas intestinal growth is stimulated by a CCK independent mechanism.

Animals↗
PubMed1997

Plasma concentrations of cholecystokinin and neurotensin in patients with cystic fibrosis.

BACKGROUND: Regulation of pancreatic exocrine secretion is controlled by vagovagal reflexes and hormones. A negative feedback control mechanism exists between the intraduodenal protease concentration and pancreatic enzyme secretion. In man cholecystokinin (CCK) is the major regulator of postprandial pancreatic enzyme secretion. There is a 50% reduction of meal-stimulated secretion by the specific CCK receptor antagonist loxiglumide, whereas atropine completely blocks postprandial secretion. Neurotensin is released postprandially by nerval reflexes and fat. It has been claimed that both hormones are increased in patients with pancreatic insufficiency. METHODS: We investigated CCK and neurotensin levels in patients with cystic fibrosis and pancreatic insufficiency. In 35 patients (2-24 years old) with cystic fibrosis with steatorrhea and in 15 patients (1.5-24 years old) with cystic fibrosis without pancreatic insufficiency pre- and post-prandial CCK and neurotensin plasma levels were measured 3 days after pancreatic enzyme therapy had been withdrawn. Nine patients (3-14 years old) who had no complaint of abdominal disease served as controls. RESULTS: Basal and postprandial CCK plasma levels did not differ statistically in the three groups, whereas basal and postprandial neurotensin levels were significantly increased in the cystic fibrosis groups. The severity of the disease had no effect on the neurotensin levels. CONCLUSIONS: Cystic fibrosis patients with severe pancreatic insufficiency did not have increased CCK plasma levels, suggesting that a CCK-mediated feedback mechanism of pancreatic enzyme secretion does not operate in our patients. In contrast, basal and postprandial neurotensin plasma levels were significantly increased in patients with cystic fibrosis but were independent of the severity of the pancreatic insufficiency.

Adolescent↗
PubMed1996

Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine.

Pancreatic proteases in the duodenum inhibit the release of cholecystokinin (CCK) and thus exert feedback control of pancreatic exocrine secretion. Exclusion of proteases from the duodenum either by the diversion of bile-pancreatic juice or by the addition of protease inhibitors stimulates exocrine pancreatic secretion. The mechanism by which pancreatic proteases in the duodenum regulate CCK secretion is unknown. In this study, we isolated a trypsin-sensitive peptide that is secreted intraduodenally, releases CCK, and stimulates pancreatic enzyme secretion in rats. This peptide was found to be identical to the porcine diazepam binding inhibitor by peptide sequencing and mass spectrometry analysis. Intraduodenal infusion of 200 ng of synthetic porcine diazepam binding inhibitor1-86 in rats significantly stimulated pancreatic amylase output. Infusion of the CCK antagonist MK-329 completely blocked the diazepam binding inhibitor-stimulated amylase secretion. Similarly, diazepam binding inhibitor33-52 [corrected] also stimulated CCK release and pancreatic secretion in a dose-dependent manner although it was 100 times less potent than the whole peptide. Using a perfusion system containing isolated mucosal cells from the proximal intestine of rats, porcine diazepam binding inhibitor 10(-12) M) dose dependently stimulated CCK secretion. In separate studies, it was demonstrated that luminal secretion of the diazepam binding inhibitor immunoreactivity (7.5 X 10(11) M) could be detected in rat's intestinal washing following the diversion of bile-pancreatic juice. The secretion of this peptide was inhibited by atropine. In conclusion, we have isolated and characterized a CCK-releasing peptide that has a sequence identical to the porcine diazepam binding inhibitor from pig intestinal mucosa and that stimulates CCK release when administered intraduodenally in rat. This peptide may mediate feedback regulation of pancreatic enzyme secretion.

Amino Acid Sequence↗
PubMed1994

Intermediate filaments in rat pancreatic acinar tumors, human ductal carcinomas, and other gastrointestinal malignancies.

BACKGROUND/AIMS: Keratin is a member of the intermediate filament family in epithelial cells. Two-dimensional gel electrophoresis of different epithelial cells has shown 20 different keratin polypeptides. Therefore, mapping of the keratin polypeptides can be used to define a specific tissue. METHODS: Cytokeratin expression was investigated by using monoclonal antibodies in human surgical specimens and autopsy material of pancreatic, gastric, liver, and colon carcinomas and cholangiocarcinomas, and their metastasis to lymph nodes and liver was examined. In addition, rat acinar cell carcinomas were used to compare cytokeratin expression in ductal vs. acinar cell pancreatic carcinomas. RESULTS: Human pancreatic ductal carcinomas expressed keratins 7, 8, 18, and 19, whereas the majority of rat acinar carcinomas did not express keratins typical for ducts in rat pancreas. The keratin patterns of gastric and colon carcinomas were identical with keratins 8, 18, and 19. In contrast, hepatocellular carcinomas expressed the same keratin pattern as pancreatic acinar carcinomas with keratins 8 and 18, whereas cholangiocarcinomas expressed keratin 7, 8, 18, and 19, similar to pancreatic ductal carcinomas. Metastasis of pancreatic ductal and colon carcinomas retained their keratin patterns. CONCLUSIONS: Keratin polypeptide typing of unknown malignant cells can be a useful tool for cell identification.

Animals↗
PubMed1994

Somatostatin inhibits CCK release by inhibiting secretion and action of CCK-releasing peptide.

We hypothesized that somatostatin exerts its inhibitory action on cholecystokinin (CCK) release and pancreatic secretion by inhibiting the secretion and/or action of a CCK-releasing peptide (CCK-RP) secreted from the small intestine. Our studies demonstrated that intravenous infusion of somatostatin (25 micrograms.kg-1.h-1) completely inhibited the increase in amylase output evoked by diversion of bile-pancreatic juice and 80 +/- 10% of the increase in plasma CCK. Intraduodenal administration of concentrated intestinal perfusate containing the CCK-RP collected from a donor rat with bile-pancreatic juice diversion raised amylase output by 2.3-fold and elevated plasma CCK levels to 7 +/- 0.8 pM in a recipient rat. The stimulatory effect of the concentrated intestinal washings was abolished when the "donor" rat was pretreated with somatostatin. In addition, in somatostatin-treated "recipient" rats, intraduodenal administration of intestinal washings containing CCK-RP also failed to elicit an increase in plasma CCK and amylase secretion. Furthermore, using duodenal mucosal explants, we demonstrated that the inhibitory action of somatostatin on CCK release evoked by CCK-RP was antagonized by pretreatment with pertussis toxin. These observations strongly suggest that somatostatin inhibits feedback regulation of pancreatic enzyme secretion by inhibiting both the secretion and action of CCK-RP.

Amylases↗
PubMed1993

Mechanism of galanin's inhibitory action on pancreatic enzyme secretion: modulation of cholinergic transmission--studies in vivo and in vitro.

This study examined the inhibitory mechanism of galanin, a 29 amino acid polypeptide on pancreatic enzyme secretion in anaesthetised rats, isolated pancreatic acini, and lobules. Urethane anaesthetised rats with pancreatic fistulas pretreated with 3-0-methyl-glucopyranose (500 mg/kg/h) were stimulated with an intravenous bolus of 2-deoxyglucose (2-DG) (75 mg/kg). Maximal amylase secretion was mean (SEM) 274 (19)% of basal secretion. Atropine (150 micrograms/kg/h) and galanin (10 nmol/kg/h) almost completely inhibited 2-DG stimulated amylase secretion suggesting an inhibition of cholinergic transmission. To further test this possibility this study investigated the effect of galanin on carbachol and cholecystokinin stimulated amylase release from isolated pancreatic acini. Galanin did not suppress carbachol or cholecystokinin stimulated amylase release, indicating that galanin inhibits exocrine secretion by indirect mechanisms. The cholinergic pathway was assessed by using pancreatic lobules containing intrapancreatic neurons. Veratridine, a sodium channel activator, dose dependently stimulated amylase release. Veratridine (100 microM) stimulated amylase release by 411 (10)% of basal secretion. Atropine (1 microM) or tetrodotoxin (1 microM) almost completely blocked veratridine stimulated amylase release. Galanin (1 microM) significantly inhibited veratridine stimulated amylase release with a maximal inhibition of 50% (p < 0.05). In addition, when lobules were incubated with [3H]-choline, galanin significantly (p < 0.05) inhibited veratridine stimulated release of newly synthesised [3H]-acetylcholine. Thus galanin inhibits pancreatic secretion by inhibiting cholinergic transmission. These studies show that galanin inhibits rat pancreatic enzyme secretion by an indirect mechanism by reducing cholinergic transmission.

Acetylcholine↗
PubMed1992

Pancreastatin inhibits pancreatic enzyme secretion by presynaptic modulation of acetylcholine release.

Pancreastatin (PST), a 49-amino acid polypeptide, inhibits endocrine and exocrine pancreatic functions. In this study, we examined the mechanism of the inhibitory action of PST on exocrine pancreatic secretion in the rat. In anesthetized rats prepared with pancreatic fistulas, intravenous administration of PST (500 pM.kg-1.h-1) completely inhibited 2-deoxyglucose (75 mg/kg)-stimulated amylase output to below basal levels. Because 2-deoxyglucose acts to stimulate the vagus, we assessed the ability of PST to inhibit carbachol-stimulated amylase release from isolated rat pancreatic acini. PST suppressed neither carbachol- nor cholecystokinin-stimulated amylase release, indicating that PST inhibits exocrine secretion via indirect mechanisms. To examine neural pathways for inhibition, we used pancreatic lobules to examine the action of PST on intrapancreatic neurons. Incubation of pancreatic lobules in 75 mM potassium buffer stimulated amylase release by a cholinergic pathway. PST dose dependently inhibited potassium-evoked amylase release, with maximal inhibition of 49.6 +/- 11%. In addition, when lobules were incubated with [3H]choline, PST inhibited KCl-stimulated release of synthesized [3H]acetylcholine by 43 +/- 5.7%. Other studies demonstrate that PST inhibits rat pancreatic enzyme secretion via presynaptic modulation of acetylcholine release.

Acetylcholine↗
PubMed1992

[Detection of mutated ras-oncogene in pancreatic cancers: improved diagnostic possibilities using molecular biology techniques?].

C-Ki-ras oncogenes have been detected by polymerase chain reaction in the majority of pancreatic carcinomas. The biological role of ras oncogenes in pancreatic carcinogenesis is unknown. This review summarizes the current knowledge of ras oncogenes in pancreatic carcinomas, the different techniques for oncogenes and their possible diagnostic value.

Cell Division↗
PubMed1991

Secretagogue response of azaserine-induced rat pancreatic acinar tumors in vivo.

This study investigates digestive and lysosomal enzyme secretion of azaserine-induced pancreatic acinar carcinomas in response to cholecystokinin in rats. After 15-20 months of treatment, 95% of the animals developed pancreatic acinar carcinomas encompassing more than 90% of the tissue. In anesthetized rats basal trypsin output was significantly elevated in the tumor group despite diminished fluid secretion. There was a linear correlation between tumor size and basal amylase and trypsin secretion. Intravenous infusion of cholecystokinin (25 IDU.kg-1.h-1) induced a significantly lower secretion of fluid per gram pancreas, as well as decreased amylase and trypsin output, in the tumor group compared with the control group. Plasma amylase and lipase levels were significantly elevated in the tumor group under both basal and stimulated conditions. The output of the lysosomal enzymes beta-D-glucuronidase and alpha-D-glucosidase was significantly increased in the tumor group under background secretin infusion. Additional cholecystokinin infusion caused a sharp increase in glucuronidase output in this group with only minimal increase in controls. Glucosidase output increased similarly in both groups. Amylase, lipase, and trypsin tumor tissue concentrations were markedly reduced by 85%, 90%, and 87%, respectively. It was concluded that the decreased secretory response of digestive enzymes may result from decreased synthesis, lowered storage capabilities, and/or a decreased/increased responsiveness to cholecystokinin. Increased glucuronidase secretion may reflect an augmented cell turnover of malignant tissue.

Adenoma↗
PubMed1990

Intracellular mechanism responsible for reduced enzyme secretion from camostate-induced hypertrophied pancreas.

Chornic exogenous administration of cholecystokinin octapeptide (CCK8) to rats led to a reduced sensitivity of pancreatic acinar cells to both CCK8 and carbachol stimulation without changes in affinity or number of CCK or muscarinic receptors. In addition, repeated feeding of camostate, a synthetic protease inhibitor which stimulates endogenous CCK release, desensitized the response of the acini to caerulein. This study investigates whether an altered postreceptor signal transduction mechanism is responsible for the reduced amylase secretion. Four days of camostate treatment significantly increased pancreatic weight, protein and amylase, but not DNA content, indicating organ hypertrophy, CCK8 and carbachol stimulated amylase release from acini, isolated from camostate-treated rats, was significantly reduced without shifting the dose response curve compared to controls. There was no difference in total phosphoinositide turnover between the groups. In addition, CCK8 and carbachol stimulated 45Ca efflux and calcium ionophore stimulated amylase release were similar in both groups. These results indicate that the release of calcium from intracellular stores and the utilization of intracellular calcium to drive amylase secretion is not affected in the hypertrophied pancreas. In contrast, incubation of acini from camostate-treated rats with TPA (a phorbol ester which directly stimulates protein kinase C) showed a 48% reduction in amylase secretion. This suggests that a regulatory mechanism is present at the level of protein kinase C or beyond, which is responsible for the decrease in amylase release in the hypertrophied pancreas.

Amylases↗
PubMed1988

In vivo action of bombesin on exocrine pancreatic secretion in the rat: independent of cholecystokinin and cholinergic mediation.

This study evaluates the effect of bombesin on pancreatic enzyme secretion in the rat and determines whether the stimulatory action of bombesin is mediated through the release of cholecystokinin (CCK) or via a cholinergic pathway. We performed in vivo experiments on conscious rats prepared with cannulae inserted in the pancreatic duct, in the external jugular vein, and in the duodenum. Intravenous infusion of bombesin stimulated pancreatic protein output in a dose-dependent fashion. Bombesin infused at 5 micrograms/kg/h stimulated pancreatic protein secretion from a basal of 12 +/- 5 to 42 +/- 10 mg/h. Infusion of proglumide (400 mg/kg/h) did not affect the stimulatory effect of bombesin on pancreatic protein secretion (38 +/- 5 mg/h). In contrast, infusion of proglumide abolished the pancreatic protein output elicited by intravenous infusion of CCK8 (500 ng/kg/h). This suggests that bombesin does not act through CCK to mediate exocrine pancreatic secretion. In separate studies we intravenously infused rats with atropine (100 micrograms/kg/h) prior to infusion with bombesin. Administration of atropine slightly decreased secretory volume but did not affect the action of bombesin. Combined administration of atropine and proglumide also did not affect pancreatic protein output stimulated by bombesin. Since infusion of neither proglumide nor atropine inhibited the stimulatory action of bombesin, the action of bombesin in the rat is probably direct and not through the release of CCK or via a cholinergic pathway.

Animals↗