Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The importance of Ca2+ in the regulation of secretion is well-known. However, recent experiments suggest that a rise in intracellular Ca2+ (Ca2+i) does not necessarily trigger secretion in pancreatic acinar cells. In AR4-2J cells the role of the Ca2+ mobilization induced by cholecystokinin/gastrin (CCK/G), which is dependent of the intracellular calcium store and the calcium influx operating through voltage-dependent calcium channels, has never been directly demonstrated. Therefore, we attempted to determine whether Ca2+i and/or extracellular Ca2+ (Ca2+e) mobilized by CCK/G plays a role in the amylase secretion of these cells. We measured the [Ca2+]i by spectrofluorometry and amylase release in different experimental procedures modulating the two pools of calcium. Ionomycin increased both [Ca2+]i and amylase related. In Ca(2+)-depleted cells or in the presence of thapsigargin the transient rise in Ca2+i and the amylase secretion induced by CCK/G were suppressed. A 50 mM K+ solution or Bay K 8644, which activated the Ca2+ influx, did not induce any variation of the basal amylase secretion. Moreover, amylase secretion induced by CCK/G did not change significantly in Ca(2+)-free medium or in the presence of nifedipine. These results indicate that in AR4-2J cells, amylase secretion is dependent of the large increase in Ca2+i induced by CCK/G and independent of the Ca2+ influx through voltage-dependent calcium channels dihydropyridine sensitive.
Pancreas 1995 Oct
PMID:Different implications of Ca2+i and and Ca2+e in CCK/gastrin-induced amylase secretion in AR4-2J cells. 857 75

Studies on cholecystokinin (CCK) receptors in rat pancreas are usually performed on homogenates. Using storage phosphor autoradiography, a new imaging technique with a high sensitivity and large linear dynamic range, we visualized and characterized CCK receptors in tissue sections of normal rat pancreas. The density of CCK receptors in pancreatic tissue sections from 10 normal rats appeared to be unevenly distributed and variable in serial sections. The binding of labeled CCK-8 was markedly inhibited by CCK-8 and CCK-A receptor antagonists, but it was only weakly affected by gastrin and CCK-B receptor antagonists. At room temperature the CCK-8 dose-inhibition curve was fitted by a two-site model: one with a high-affinity but low-capacity site and another with a low-affinity but high-capacity site. The CCK-8 dose-inhibition curve showed that the inhibition of the variable high-density receptors took place at a low concentration of CCK-8, while the diffuse low-density receptors were inhibited at the high concentration of 1 microM CCK-8. Binding of labeled CCK-8 at 37 degrees C was homogeneous with a low affinity and comprised only 4% of that found at room temperature. In summary, an uneven density of CCK receptors in the rat exocrine pancreas was observed and attributed to the variable expression of high-affinity CCK receptors in pancreatic acini.
Pancreas 1996 Oct
PMID:Visualization and characterization of CCK receptors in exocrine pancreas of rat with storage phosphor autoradiography. 888 54

The mechanisms underlying the insulinotropic action of gastrin releasing peptide (GRP) were examined in normal mouse islets. GRP (100 nM) enhanced insulin secretion at glucose concentrations of > or = 11.1 mM (p < 0.05) but only in the presence of extracellular Ca2+. The insulinotropic effect of the peptide studied during perifusion at 16.7 mM glucose was transient and vanished in time. GRP stimulated, transiently, 45Ca2+ efflux from 45Ca(2+)-prelabeled islets, both in the presence and in the absence of extracellular Ca2+ (p < 0.05), suggesting that GRP releases Ca2+ from intracellular stores. Similarly, GRP increased 86Rb+ efflux from 86Rb(+)-prelabeled islets both in the presence and in the absence of extracellular Ca2+ (p < 0.001). In contrast to GRP-induced insulin secretion, the GRP-induced 86Rb+ efflux was sustained throughout the stimulation period, suggesting that increased K+ conductance may be involved in the vanishing effect of GRP on insulin secretion. Furthermore, both inhibition of protein kinase C (PKC) by staurosporine (1-10 microM) and down-regulation of PKC activity by long-term incubation with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate inhibited GRP-stimulated insulin secretion (p < 0.05). These results indicate that GRP activates PKC by an action involving liberation of Ca2+ from Ca2+ stores. Therefore, also the influence of GRP on phosphoinositide hydrolysis was studied by means of 3H efflux from myo-[2-3H]inositol prelabeled islets. However, GRP did not stimulate the 3H efflux. In contrast, GRP-stimulated insulin secretion was abolished by an inhibitor of phospholipase D, wortmannin (1 microM). The results suggest that GRP transiently potentiates glucose-induced insulin secretion by an action mediated by PKC activated by diacylglycerol formed through activation of phospholipase D. Simultaneously, an as yet unknown mechanism liberating Ca2+ from intracellular stores is activated.
Pancreas 1996 Jan
PMID:Studies on the mechanisms by which gastrin releasing peptide potentiates glucose-induced insulin secretion from mouse islets. 892 19

In adult rats, cholecystokinin (CCK) binds to pancreatic CCK-A receptors and stimulates exocrine secretion and pancreatic growth. In newborn rats there is very little mature intestinal CCK and few pancreatic CCK-A receptors. However, there is an abundant source of the related peptide gastrin, and in addition, there are pancreatic CCK-B/gastrin receptors. In this study, we have explored the hypothesis that gastrin may "deputise" for CCK in the neonate and cause pancreatic exocrine secretion, growth, and maturation. Newborn rats were injected intraperitoneally with the gastrin antagonist, C1-988, or placebo for 5 days and sacrificed on day 6. Body weight (CI-988, 8.25 +/- 0.48 g; placebo, 10.17 +/- 0.93 g) and pancreatic weight (19.41 +/- 1.5 vs. 21.58 +/- 1.72 mg) were the same. Protein (1,202 +/- 78 vs. 1,254 +/- 56 micrograms), amylase (22.3 +/- 0.9 vs. 19.2 +/- 1.00 U), RNA (117 +/- 7 vs. 126 +/- 5 micrograms), and DNA (95 +/- 8 vs. 100 +/- 7 micrograms) contents of the pancreas were similar in the two groups. The weight of the stomach was reduced (p = 0.04) in the treated group (50.8 +/- 2.5 mg) compared to the placebo group (59.8 +/- 3.7 mg). In both neonates and adults, CCK-8 was approximately 1,000 times more potent than gastrin-17 in stimulating amylase release from isolated pancreatic acini. This suggests that enzyme release is probably mediated by the same receptors in both adults and neonates, and in adults previous work has shown this to be the CCK-A receptor. In conclusion, these data show that gastrin has very weak effects on neonatal pancreatic exocrine secretion, and furthermore, gastrin is not essential for growth and maturation of the neonatal pancreas. The role of gastrin and CCK-B/gastrin receptors in the neonatal pancreas remains speculative.
Pancreas 1997 Apr
PMID:Gastrin effects on growth and exocrine secretion in the neonatal rat pancreas. 909 62

Growth of the human pancreatic carcinoma cell line KP-1N was stimulated with cholecystokinin (CCK)-8. A 40% increase in cell numbers was observed in the presence of 10(-10) MCCK-8 and this increase was inhibited by the addition of 25 microM CCK-A receptor antagonist (CR1505). The binding affinity of CCK-8 to KP-1N cells was 21-fold higher than that of gastrin 17-I. No significant increase in intracellular Ca2+ concentration was found upon stimulation with CCK-8. Components of signal transduction pathways that were activated in KP-1N cells after stimulation with CCK-8 were studied. CCK-8 stimulated tyrosine phosphorylation of a mitogen-activated protein kinase (MAPK) of approximately 42 kDa (p42map). c-Jun amino-terminal kinases (JNKs) of 46 kDa (p46jnk) and 55 kDa (p55jnk) were also activated by CCK-8 and increased the phosphorylation of c-Jun. CCK-8 at 10(-7) M induced 1.5-fold increases in the phosphorylation of MAPK and of c-Jun by JNKs, respectively. These results suggest that cell proliferation stimulated with CCK-8 in KP-1N cells may be mediated by signal transduction cascades leading to activation of JNKs and MAPKs.
Pancreas 1998 May
PMID:Jun and MAP kinases are activated by cholecystokinin in the pancreatic carcinoma cell line KP-1N. 959 11

Major features of pancreatic secretion stimulated by a meal depend on intestinal phase mechanisms. However, an intrajejunal (i.j.) meal infusion is widely used for the treatment of inflammatory pancreatic diseases when the resting of the gland is desired. This study was undertaken to compare the effects of an intragastric (i.g.) and an i.j. complete fluid (Lundh) test meal on pancreatic enzyme secretion. Eight men (mean age, 43 years; range, 31-48) free from pancreatic disease were studied. Pancreatic secretion was measured via a multiple-lumen tube by aspiration of the duodenal juice. After a fasting period, the Lundh test meal was placed in the stomach or the upper jejunum. After the i.g. administration of the test meal, the aspirated duodenal juice was reinfused into the jejunum. The effect of atropine infusion (0.5 microg/kg/h) on the pancreatic enzyme secretion was studied. The pancreatic amylase, trypsin, and lipase outputs were determined. The plasma levels of cholecystokinin (CCK) and of gastrin were measured by bioassay and radioimmunoassay, respectively. The trypsin, amylase, and lipase secretions increased significantly after either an i.g. or an i.j. test meal intake. The trypsin, amylase, and lipase outputs were significantly decreased during the i.j. perfusion as compared with i.g. administration. The gastrin levels increased significantly after i.g., but remained unchanged after i.j. administration. The CCK release attained its maximum 40 and 60 min after the i.g. and i.j. test meal, respectively. However, the CCK release was significantly lower during the i.j. administration as compared with i.g. perfusion. An atropine infusion significantly reduced the i.g. and i.j. test meal-stimulated enzyme outputs. An i.j.-administered meal stimulates the pancreatic enzyme secretion, but this effect is significantly lower than that which occurs on i.g. administration. The i.j. meal-stimulated secretion of pancreatic enzymes is subject to both cholinergic and peptidergic regulation. The deficiency of gastrin and the delayed and decreased CCK release are believed to account for the reduced enzyme output.
Pancreas 1999 Mar
PMID:Effect of a liquid meal given as a bolus into the jejunum on human pancreatic secretion. 1009 Apr 18

A CCK-deficient mouse mutant generated by gene targeting in embryonic stem cells was analyzed to determine the importance of CCK for growth and function of the exocrine pancreas and for pancreatic adaptation to dietary changes. RIAs confirmed the absence of CCK in mutant mice and demonstrated that tissue concentrations of the related peptide gastrin were normal. CCK-deficient mice are viable and fertile and exhibit normal body weight. Pancreas weight and cellular morphology appeared normal, although pancreatic amylase content was elevated in CCK-deficient mice. We found that a high-protein diet increased pancreatic weight, protein, DNA, and chymotrypsinogen content similarly in CCK-deficient and wild-type mice. This result demonstrates that CCK is not required for protein-induced pancreatic hypertrophy and increased proteolytic enzyme content. This is a novel finding, since CCK has been considered the primary mediator of dietary protein-induced changes in the pancreas. Altered somatostatin concentrations in brain and duodenum of CCK-deficient mice suggest that other regulatory pathways are modified to compensate for the CCK deficiency.
 ...
PMID:Pancreatic function in CCK-deficient mice: adaptation to dietary protein does not require CCK. 1033 22

We have reported that cholecystokinin-like immunoreactivity (CCK-LI) and its transcripts are expressed in rat pancreatic islets (Endocrinology 1998;139:389-96). The purpose of this study was to elucidate the ontogeny of CCK during pancreatic development in the rat. Fetal rats from day 13 (E13) to 20 (E20) and postnatal (P) rats from day 1 to adulthood were used in this study. Immunohistochemical studies of rat pancreas were carried out with rabbit antisera against CCK-8 and gastrin-17. The absorption studies were performed by using CCK-8 antiserum incubated with excess CCK-8 or gastrin-17. In situ hybridization was performed to demonstrate the CCK and gastrin transcripts in the pancreas. CCK and gastrin were first detected at E15, and they were distributed in the periphery of the islets in the fetal and neonatal pancreas. The mirror sections for CCK revealed positive cells with characteristics identical to those that stained positive for gastrin. The CCK-LI in early development was completely abolished by preabsorption with excess gastrin but not with CCK-8. These findings indicated that the CCK-LI in the fetal and neonatal pancreas was crossreacting gastrin rather than CCK-8. From weaning (P21) through adulthood, on the other hand, CCK-LI was expressed diffusely in pancreatic islets, but there were no gastrin-positive cells after weaning. In situ hybridization showed that CCK messenger RNA (mRNA) was present in rat pancreatic islets in adults but not in early development. Although CCK-positive cells were not detected in fetal and neonatal pancreatic islets, CCK was expressed in islets during and after weaning through adulthood, indicating that CCK in pancreatic islets might be developmentally regulated.
Pancreas 1999 Jul
PMID:Expression of cholecystokinin in the pancreas during development. 1041 99

The acute effects of kidney bean (Phaseolus vulgaris) E2L2 lectins (PHA) given orally to conscious rats or continually infused into the duodenum of anesthetized rats on blood cholecystokinin (CCK), secretin, and gastrin and on secretion of pancreatic digestive enzymes have been evaluated. PHA increased circulating levels of CCK and secretin but did not alter gastrin. In addition, PHA induced dose-dependent secretion of trypsinogen, chymotrypsinogen, and alpha-amylase by the pancreas in vivo. This pancreas output appeared to be modulated only in part through CCK. Thus pretreatment of rats with a CCK-A receptor antagonist (L-364718) attenuated the immediate (< or = 90 min) pancreas secretory response to PHA but could not prevent a PHA-associated increase in digestive enzyme output in the longer term (after 90 min). In contrast, treatment of rats with L-364718 abolished the stimulatory effects of soyabean trypsin inhibitors on digestive enzyme secretion in both the short and long term. Additional mechanisms or hormones, such as secretin, may play a role in modulating later exocrine pancreas responses to PHA.
Pancreas 1999 Nov
PMID:Secretion of pancreatic digestive enzymes induced in rats by first-time oral exposure to kidney bean E2L2 lectin is mediated only in part by cholecystokinin (CCK). 1054 99

Pancreaticobiliary diversion (PBD) and biliodigestive shunt (BDS) cause long-standing hypercholecystokininemia followed by pancreatic hyperplasia. These changes have been suggested to be due to the lack of intraluminal trypsin and bile, respectively, in the upper small intestine. The aim of these experiments was to study the effect of restoration of intraluminal trypsin and bile on plasma levels of cholecystokinin (CCK) and the changes found in exocrine and endocrine pancreas after PBD and BDS. Male Sprague-Dawley rats were used. PBD was done in 16 rats, eight of which had trypsin dissolved in 50 mM sodium bicarbonate (SB), and eight had SB only by gastric intubation twice daily. BDS was done in another 16 rats, eight of which had bile dissolved in SB, and eight had SB in a similar manner. Sham-operated rats had SB and served as controls. After 4 weeks, the rats were killed, and the concentrations of circulating CCK, gastrin, glucose, glucagon, and insulin were determined. The pancreas was removed, weighed, and analyzed for contents of water, protein, and DNA. In another study, PBD-operated rats got trypsin in varying dosages or trypsin and taurocholate in combination for 2 weeks before death. The concentrations of plasma CCK and glucagon were elevated after both PBD and BDS. PBD decreased the concentration of gastrin in plasma. PBD caused an increase of pancreatic weight and the contents of protein and DNA. Trypsin substitution to PBD-operated rats did not affect plasma CCK or glucagon levels, but the PBD-induced increases in weight and DNA content were counteracted by trypsin. Higher dosages of trypsin did not further influence the effects seen after PBD. Pancreatic weight and DNA content were increased after BDS. Bile administration completely abolished the increase in plasma CCK and glucagon, as well as the gain in pancreatic weight, and reduced the increase in pancreatic DNA. Substitution with bile to BDS-operated rats abolished the increase in the plasma levels of CCK and glucagon, as well as the trophic effects on the pancreas. Trypsin substitution to PBD-operated rats partly reversed the trophic effects on the pancreas but not the hormonal changes in plasma. Thus the trophic effects on the pancreas exerted by BDS seem to be dependent on the lack of bile in the upper small intestine, whereas the effects of PBD only partly are a consequence of the absence of intraluminal trypsin.
Pancreas 2000 Mar
PMID:Effects of intraluminal trypsin and bile on the exocrine and endocrine pancreas after pancreaticobiliary diversion and biliodigestive shunt. 1070 33


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