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)

A number of regulatory peptides were investigated for their ability to elevate plasma cAMP. Pituitary adenylate cyclase activating peptide (PACAP)-27, PACAP-38, helodermin, helospectin I and II, vasoactive intestinal peptide (VIP), glucagon, parathyroid hormone (PTH), calcitonin and calcitonin gene-related peptide were among the peptides that were highly effective in raising plasma cAMP when given intravenously in equimolar doses to conscious mice. PACAP-27 and -38 were more effective than any of the other peptides. PACAP 16-38, secretin, gastrin-17, galanin, somatostatin, cholecystokinin-8s, pancreatic polypeptide, substance P, peptide YY and neuropeptide Y were inactive and also did not interfere with the PACAP-27-evoked rise in plasma cAMP levels. Repeated injections of PACAP-27 every 30 min caused a progressive reduction in the plasma cAMP response (measured 5 min after each injection). Forskolin, an activator of adenylate cyclase, dose-dependently raised the plasma concentration of cAMP and displayed a synergistic effect when given in a low dose concurrently with PTH or PACAP-38. The phosphodiesterase inhibitor rolipram dose-dependently raised the plasma concentration of cAMP. Combined treatment with PACAP-27 and a threshold dose of rolipram resulted in an exaggerated plasma cAMP response. Kidney hilus ligation suppressed the responses to PACAP-38, PTH, helodermin, helospectin, VIP, glucagon and calcitonin. Hepatectomy suppressed the response to glucagon but was without effect on the response to the other peptides. Pancreatectomy and spleenectomy reduced the response to VIP, but was without effect on the response to the other peptides. PACAP-27 stimulated cAMP efflux from the isolated rat tail vein. Hence, it cannot be excluded that blood vessels contribute to the peptide evoked plasma cAMP response in vivo.
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PMID:Neuropeptides of the vasoactive intestinal peptide/helodermin/pituitary adenylate cyclase activating peptide family elevate plasma cAMP in mice: comparison with a range of other regulatory peptides. 133 41

Receptor-dependent and -independent regulation of gastrin secretion from cultured human antral G cells was investigated. Human antral mucosal cell preparations that were enriched for G cells were obtained by sequential incubations with collagenase and ethylenediaminetetraacetic acid, centrifugal elutriation, and short-term culture. After a 2-day incubation period, gastrin- and somatostatin-containing cells accounted for 15% and 5%, respectively, of the total adhered-cell population. Forskolin, A23187, and beta-phorbol 12 myristate 13-acetate stimulated basal gastrin secretion from cultured human G cells in a concentration-dependent fashion. These results indicate that gastrin release could be mediated by elevations in cytosolic cyclic adenosine monophosphate levels, calcium influx, or activation of protein kinase C. A direct stimulatory role for bombesin- and gastrin-releasing peptide was supported by experiments showing concentration-dependent enhancement of gastrin release by bombesin from 0.01 fmol/L to 10 nmol/L. The putative bombesin antagonist [Leu13-psi-CH2NH-Leu14] bombesin augmented basal gastrin levels by itself and produced weak inhibition of bombesin-induced gastrin secretion from human antral G cells. Somatostatin potently suppressed forskolin- and bombesin-mediated gastrin release but did not significantly alter basal gastrin levels. These results suggest that bombesin and somatostatin directly activate and inhibit G-cell function via specific and sensitive receptors. Furthermore, the adenylate cyclase and phosphatidyl inositide second messenger systems seem to be intracellular mediators of gastrin secretion from human antral G cells.
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PMID:Gastrin secretion from human antral G cells in culture. 197 10

A primary culture of human antral somatostatin cells has been developed and used in release studies. The phorbol ester, phorbol 12 myristate 13-acetate, caused a concentration-dependent increase in immunoreactive somatostatin secretion with a 1-mumol/L concentration resulting in a 40-fold stimulation (basal 0.28% +/- 0.7% total cell content vs. 13.8% +/- 2.2% TCC, P less than 0.005). The calcium ionophore, A23187, resulted in a significant stimulation only at 1 mumol/L (basal 0.28% +/- 0.7% TCC vs. 2.2% +/- 0.5% total cell content, P less than 0.05). However, addition of the ionophore at 1 mumol/L with the phorbol ester resulted in a potentiation of the response at all concentrations tested. Removal of extracellular calcium by chelation with EGTA reduced the response to that seen with the phorbol ester alone. Forskolin at 0.1 mmol/L resulted in a five-fold increase (basal 0.6% +/- 0.2% total cell content vs. 2.8% +/- 0.9% total cell content, P less than 0.02) and was 1000-fold less potent than the phorbol ester. The peptides bombesin and gastrin at concentrations up to 1 mumol/L had no effect on basal secretion. Cholecystokinin-8 significantly stimulated somatostatin secretion with a maximal effect at 0.1 mumol/L resulting in an eightfold increase (basal 0.2% +/- 0.04% total cell content vs. 1.5% +/- 0.4% total cell content, P less than 0.02). These results indicate that human antral D cells are more responsive to agents acting through the c-kinase pathway (phorbol 12 myristate 13-acetate, A23187, and cholecystokinin) than adenylate cyclase (forskolin).
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PMID:Release of somatostatin immunoreactivity from human antral D cells in culture. 197 18

The effects of adenosine on gastrin release were studied in enzymatically dispersed canine antral cells after 24-36 h in primary culture. We found two contrasting actions for adenosine: inhibition of forskolin-stimulated gastrin release and potentiation of bombesin-stimulated gastrin release. These actions appeared to be mediated by A1 and A2 receptors, respectively. Forskolin-stimulated gastrin release was reduced by adenosine and the A1-selective agonist N6-(L-2-phenylisopropyl)adenosine (L-PIA) but not by the A2-selective agonist 2-phenylaminoadenosine (CV 1808). This inhibition by adenosine was reversed by the preferential A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) as well as by the nonselective adenosine receptor antagonist 8-phenyltheophylline (8-PT). Incubation of the cells with pertussis toxin (200 ng, 8 h) reversed the inhibition by adenosine. In contrast, bombesin stimulation of gastrin release was potentiated by adenosine and CV 1808 but not altered by L-PIA. This effect was enhanced by DPCPX and was not altered by treatment of cells with pertussis toxin. In the absence of exogenous adenosine, 8-PT and DPCPX produced a small increase in basal and stimulated gastrin release. These data suggest dual modulation by adenosine of G-cell function. A1 receptors inhibit adenosine 3,5'-cyclic monophosphate (cAMP)-mediated gastrin release via a pertussis toxin-sensitive mechanism, whereas A2 receptors potentiated the response to cAMP-independent stimuli of gastrin release. Enhancement of gastrin release by adenosine antagonists suggests functional restraint by endogenous adenosine.
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PMID:Dual modulation by adenosine of gastrin release from canine G-cells in primary culture. 222 Oct 65

Cellular mechanisms underlying the anti-secretory actions of the prostaglandin E2 analogue enprostil were studied using enzyme-dispersed, elutriator-enriched canine parietal cells and the accumulation of the weak base 14C-labeled aminopyrine as a functional index. Enprostil inhibited the accumulation of aminopyrine stimulated by histamine and the phosphodiesterase inhibitor isobutylmethyl, but not by carbachol, gastrin, or dibutyryl cyclic adenosine monophosphate. Inhibition by enprostil was dose-dependent (0.1 nM to 1 microM), with maximal inhibition ranging from 65 to 95 percent. Over the same concentration range, enprostil inhibited the histamine-stimulated generation of cyclic adenosine monophosphate. This selective inhibition of histamine activation of parietal cell function was comparable to that found for prostaglandin E2. Forskolin, a diterpene that directly activates the catalytic subunit of adenylate cyclase, was also markedly inhibited by nanomolar concentrations of prostaglandin E2 and enprostil. We conclude that at least a component of the secretory inhibition by enprostil reflects direct interference with histamine stimulation of parietal cell adenylate cyclase.
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PMID:Prostanoid inhibition of canine parietal cells. 242 41

The diterpene, forskolin, direct activator of the catalytic subunit of the adenylate cyclase from various tissues, also stimulates gastric acid secretion: in vitro, with an isolated parietal cell preparation, forskolin dose-dependently stimulated acid secretion (EC50: 1 microM) (measured by accumulation in the acidic spaces of the weak base [14C]-aminopyrine) and the maximal acid secretory value at 0.1 mM was 4 times higher than that obtained with histamine. Forskolin dramatically increased the production of intracellular cyclic-AMP at a level 4 times higher than that obtained with histamine at the same concentration. In vivo, gastric acid secretion of the rat is dose-dependently increased. The doses required to get a significant response (100 nmol/kg) were 1,000 times higher than those required for gastrin and 100 times lower than those for histamine, but the same maximal value was obtained. Cimetidine did not significantly modified this response. These results demonstrate that, both in vitro and in vivo, forskolin is a potent stimulant for gastric acid secretion.
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PMID:[Is forskolin a stimulant of gastric secretion?]. 285 29

Prostaglandin E (PGE) potently inhibits acid secretion stimulated by histamine, but not by acetylcholine or gastrin, and is accompanied by decreased intracellular cAMP. Adenylate cyclase receptor systems are composed of three complex proteins: cell receptor, nucleotide binding protein, and the catalytic subunit. The exact mechanism of PGE interaction with this complex remains unclear and elucidation of this site of action is the purpose of this study. We utilized molecular probes directed at the various components of adenylate cyclase. Cholera toxin alters the stimulatory subunit of the nucleotide binding proteins (Ns), rendering it resistant to normal deactivation, whereas N-ethylmaleimide (NEM) blocks the inhibitory subunit (Ni). Forskolin acts as a direct activator of the catalytic subunit of adenylate cyclase and 8-bromo-cAMP acts as a cyclic AMP mimetic. We measured in vitro acid secretion in isolated parietal cells by the assessment of [14C]aminopyrine (AP) accumulation. The PGE1 analog (miso) and the PGE2 analog (DMPG) were incubated in graded doses (10(-11) to 10(-6) M) with histamine (10(-6) M). Miso (10(-7) M) reduced AP accumulation to 21 +/- 8% of histamine alone (100%) and DMPG (10(-6) M) reduced AP to 61 +/- 9% (P less than 0.005 for both). AP accumulation stimulated by 8-Br-cAMP (10(-6) M) and forskolin (10(-6) M) was not significantly affected by either PGE analog (P greater than 0.05) suggesting that the site of PGE interaction is proximal to the activation of the catalytic subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin inhibition of acid is cAMP dependent. 303 81

In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by cultured cells from a human gastrinoma. In all GH-secreting adenomas and in rat anterior pituitary cells, RC-160 was the most potent compound. RC-160 significantly inhibited GH-, PRL, and/or alpha-subunit release by human GH-secreting pituitary adenoma cells in concentrations as low as 10(-12)-10(-14) M, whereas at the same concentrations, octreotide and BIM-23014 did not inhibit or were significantly less effective in inhibiting GH release (P < 0.01, RC-160 vs. octreotide and BIM-23014). In rat anterior pituitary cell cultures, the IC50 values for inhibition of GH release were, in rank order of potency, 0.1, 5.3, 47, 48, and 99 pM for RC-160, SS-14, BIM-23014, octreotide, and SS-28, respectively. Maximal inhibitory effects by the three analogs were the same in the human GH adenoma cell cultures and the rat anterior pituitary cell cultures (-60%). On the basis of these data, RC-160 appears to be about 500 times more potent than octreotide and BIM-23014 in inhibiting GH release by rat anterior pituitary cells in vitro. Forskolin (100 microM) as well as pretreatment of the cells with pertussis toxin significantly diminished the inhibitory effects of the three SS analogs and those of SS-14 and SS-28 to the same extent. The latter data suggest that octreotide, RC-160, and BIM-23014 act mainly via a pertussis toxin-sensitive G-protein and an adenylyl cyclase-dependent mechanism. In the human gastrinoma culture, RC-160 inhibited gastrin release significantly more than octreotide at 10(-12)- and 10(-14)-M concentrations (P < 0.01). In conclusion, the SS analogs octreotide, RC-160, and BIM-23014 may have significant different potencies of inhibition of hormone release in vitro, with RC-160 being the most potent SS analog and octreotide and BIM-23014 having similar potencies. Depending on the pharmacokinetic properties of these three octapeptide SS analogs, these observations may have consequences for the medical therapy of patients with SS receptor-positive endocrine tumors.
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PMID:Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on the inhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells. 790 31

ECL cells are numerous in the acid-producing part of the rat stomach. They are rich in histamine and pancreastatin, a chromogranin A-derived peptide, and they secrete these products in response to gastrin. We have examined how isolated ECL cells respond to a variety of neuromessengers and peptide hormones. Highly purified (85%) ECL cells were collected from rat stomach using repeated counter-flow elutriation and cultured for 48 h before experiments were conducted. The ECL cells responded to gastrin, sulphated cholecystokinin-8 and to high K+ and Ca2+ with the parallel secretion of histamine and pancreastatin. Glycine-extended gastrin was without effect. Forskolin, an activator of adenylate cyclase, induced secretion, whereas isobutylmethylxanthine, a phosphodiesterase inhibitor, raised the basal release without enhancing the gastrin-evoked stimulation. Maximum stimulation with gastrin resulted in the release of 30% of the secretory products. Numerous neuromessengers and peptide hormones were screened for their ability to stimulate secretion and to inhibit gastrin-stimulated secretion. Pituitary adenylate cyclase activating peptide (PACAP)-27 and -38 stimulated secretion of both histamine and pancreastatin with a potency greater than that of gastrin and with the same efficacy. Related peptides, such as vasoactive intestinal peptide, helodermin and helospectin, stimulated secretion with lower potency. The combination of EC100 gastrin and EC50 PACAP produced a greater response than gastrin alone. None of the other neuropeptides or peptide hormones tested stimulated secretion. Serotonin, adrenaline, noradrenaline and isoprenaline induced moderate secretion at high concentrations. Muscarinic receptor agonists did not stimulate secretion, and histamine and selective histamine receptor agonists and antagonists were without effect. This was the case also with GABA, aspartate and glutamate. Somatostatin and galanin, but none of the other agents tested, inhibited gastrin-stimulated secretion. Our results reveal that not only gastrin but also PACAP is a powerful excitant of the ECL cells, that not only somatostatin, but also galanin can suppress secretion, that muscarinic receptor agonists fail to evoke secretion, and that histamine (and pancreastatin) does not evoke autofeedback inhibition.
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PMID:Neurohormonal regulation of histamine and pancreastatin secretion from isolated rat stomach ECL cells. 941 89

The PICM-19 fetal liver cell line was isolated from the primary culture and spontaneous differentiation of pig epiblast cells, i.e. embryonic stem cells. PICM-19 cells were induced to differentiate into mostly ductular formations by culturing at pH 7.6-7.8. The ductules were functionally assayed by treatment with cAMP inducing agents and bioactive peptides reported to influence the secretory activity of liver bile ductules. The secretory response of the cells was assessed by qualitative or quantitative measurement of the cross-sectional area of the ductal lumens and the appearance of biliary canaliculi in between PICM-19 cells that had formed monolayers instead of ducts. Forskolin (10 microM) and 8-bromoadenosine 3':5'-cyclic monophosphate (bcAMP; 2 mM) stimulated fluid transport and expansion of ductal structures in 15-20 min and stimulated the appearance and expansion of biliary canaliculi in 30-60 min. Cholera toxin (50 ng/ml) stimulates fluid transport in both ductules and canaliculi in 1-2 h, while 8-bromoguanosine 3':5'-cyclic monophosphate (bcGMP; 2 mM) stimulated only biliary canaliculi in 2 h. Glucagon (1.4 nM) produced a similar response in 5-10 min in ductal structures only, but the response was transitory and was almost completely reversed within 30 min. Secretin (100 pM) and vasoactive intestinal peptide (75 pM) produced a sustained response with maximal ductal lumen expansion occurring in 5-10 min and neither had an immediate effect on canaliculi. Somatostatin (0.5 microM) and gastrin (1 microM) caused marked reduction or disappearance of ductal lumens in 30-60 min, but was ineffective in reversing secretin (100 nM)-induced duct distension. Application of the adrenergic agonists, epinephrine, isoproterenol, and phenylephrine (100 microM), resulted in the complete shrinkage of ductal lumens in 20-30 min. A shift to pH 7.0-7.2 resulted in almost complete reduction of ductal lumens, while a shift to pH 7.8-8.0 resulted in expansion, although not full expansion, of the ductal lumens. PICM-19 bile duct cultures were positive for cytokeratin-7, aquaporin-1 and aquaporin-9 by Western blot analysis. The amounts of these proteins increased in the cultures as differentiation proceeded over time. Transmission electron microscopy revealed that the ductal structures were usually sandwiched between SIM mouse, thioguanine- and ouabain-resistant (STO) feeder cells that had produced a collagen matrix. Also, the ductular PICM-19 cells possessed cilia, probably occurring as a single cilium in each cell, that projected into the lumens of the ducts. The results indicated that the in vitro-produced ductal structures of the PICM-19 cell line are a functional model for biliary epithelium.
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PMID:The PICM-19 cell line as an in vitro model of liver bile ductules: effects of cAMP inducers, biopeptides and pH. 1209 33


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