Gastrin mediates the gastric mucosal proliferative response to feeding

1996 ◽  
Vol 271 (3) ◽  
pp. G470-G476 ◽  
Author(s):  
G. V. Ohning ◽  
H. C. Wong ◽  
K. C. Lloyd ◽  
J. H. Walsh
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Pancreatic Secretion ◽  
Proliferative Response ◽  
Male Rats ◽  
Oxyntic Mucosa ◽  
Proliferative Zone ◽  
Mucosal Proliferation

The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat.

Role of gastrin/CCK-B receptors in meal-stimulated acid secretion in rats

1997 ◽  
Vol 272 (5) ◽  
pp. G1243-G1248 ◽  
Author(s):  
K. Aurang ◽  
C. F. Spraggs ◽  
C. Jordan ◽  
K. C. Lloyd
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Rat Model ◽  
Acid Output ◽  
Male Rats ◽  
Plasma Histamine ◽  
Plasma Gastrin

Gastrin is the principal hormonal mediator of gastric acid secretion. Using an in vivo, intact, anesthetized rat model, we studied the role of gastrin/cholecystokinin (CCK)-B receptors in regulating the release of histamine and somatostatin during intragastric stimulation of acid secretion during a peptone meal. In pylorusligated, adult male rats (each implanted with a gastric cannula and portal venous and splenic artery catheters), after a 30-min basal period, gastric acid secretion was stimulated for 90 min either by an intravenous infusion of gastrin-17 (15 micrograms.kg-1.h-1) or by extragastric titration of 5 ml 8% peptone meal at pH 5.5. Basal and stimulated acid outputs and portal venous plasma gastrin, histamine, and somatostatin concentrations were measured before and after close-arterial injection of a new, relatively selective, gastrin/CCK-B receptor antagonist GR143330X. GR143330X reduced basal acid output by 50% but not basal plasma gastrin, histamine, or somatostatin concentrations. GR143330X reduced gastrin-stimulated acid output by 80%, plasma histamine by 70%, and plasma somatostatin by 34%. During intragastric peptone meal stimulation GR143330X reduced the acid response by 42% during the 30- to 60-min period but not during the 60- to 90-min period. GR143330X reduced the plasma histamine response by 72 and 68%, and the plasma somatostatin response by 32 and 54% during the 30- to 60- and 60- to 90-min periods, respectively. GR143330X did not block the gastrin response to peptone at any time. These results indicate that GR143330X is an effective agent for blocking gastrin-stimulated acid secretion and histamine and somatostatin release in rats. Furthermore, we show for the first time in an intact, in vivo, anesthetized rat model that meal-stimulated activation of gastrin/CCK-B receptors stimulates acid secretion in part by regulating the release of histamine and somatostatin.

Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands

2005 ◽  
Vol 289 (6) ◽  
pp. G1061-G1066 ◽  
Author(s):  
Anna Berg ◽  
Stefan Redéen ◽  
Magnus Grenegård ◽  
Ann-Charlott Ericson ◽  
Sven Erik Sjöstrand
Keyword(s):  
Nitric Oxide ◽  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Enzymatic Digestion ◽  
Human Gastric Mucosa ◽  
Gastric Glands ◽  
Oxyntic Mucosa ◽  
No Donor

We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso- N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4 H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

Radioreceptor and biological characterization of cholecystokinin and gastrin in the chicken

1984 ◽  
Vol 246 (3) ◽  
pp. G296-G304
Author(s):  
S. R. Vigna
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Amylase Secretion ◽  
Physiological Regulation ◽  
Chicken Brain ◽  
Specific Radioimmunoassay ◽  
Cck Receptor Antagonist

Radioimmunoassay, radioreceptor assays, and bioassays were used to demonstrate that chicken brain and antrum extracts contain cholecystokinin (CCK)-like and gastrinlike peptides, respectively. C-terminal-specific radioimmunoassay of partially purified chicken CCK and gastrin gave dilution curves parallel to those of the mammalian peptides. Mouse cerebral cortical and rat pancreatic membrane radioreceptor assays were used to differentiate CCK- from gastrinlike peptides on the basis of the different CCK versus gastrin specificities of the two receptors. Confirmation of the biological activity of chicken brain CCK was obtained by stimulation of amylase secretion from rat pancreatic lobules in vitro. The specificity of this response was demonstrated by the inhibition of chicken CCK-stimulated amylase secretion by the specific CCK receptor antagonist dibutyryl cGMP. Chicken antral gastrin stimulated gastric acid secretion from the rat stomach in vivo. In contrast to previous hypotheses, it is proposed that chickens have significant amounts of an antral gastrinlike peptide and that therefore it is possible that gastrin is involved in the physiological regulation of gastric acid secretion in chickens.

Neuronal nitric oxide synthase: expression in rat parietal cells

2001 ◽  
Vol 280 (2) ◽  
pp. G308-G313 ◽  
Author(s):  
Shyamal Premaratne ◽  
Chun Xue ◽  
John M. McCarty ◽  
Muhammad Zaki ◽  
Robert W. McCuen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Intracellular Signaling ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Parietal Cells ◽  
Nadph Diaphorase ◽  
Rt Pcr ◽  
Oxyntic Mucosa

Nitric oxide synthases (NOS) are enzymes that catalyze the generation of nitric oxide (NO) from l-arginine and require nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. At least three isoforms of NOS have been identified: neuronal NOS (nNOS or NOS I), inducible NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS II). Recent studies implicate NO in the regulation of gastric acid secretion. The aim of the present study was to localize the cellular distribution and characterize the isoform of NOS present in oxyntic mucosa. Oxyntic mucosal segments from rat stomach were stained by the NADPH-diaphorase reaction and with isoform-specific NOS antibodies. The expression of NOS in isolated, highly enriched (>98%) rat parietal cells was examined by immunohistochemistry, Western blot analysis, and RT-PCR. In oxyntic mucosa, histochemical staining revealed NADPH-diaphorase and nNOS immunoreactivity in cells in the midportion of the glands, which were identified as parietal cells in hematoxylin and eosin-stained step sections. In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR. Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity). Expression of nNOS in parietal cells suggests that endogenous NO, acting as an intracellular signaling molecule, may participate in the regulation of gastric acid secretion.

Relationship between maternal milk PGE2 and gastric acid secretion in newborn rats

1990 ◽  
Vol 259 (5) ◽  
pp. G702-G708
Author(s):  
A. Wirbel ◽  
R. Ducroc ◽  
B. Garzon ◽  
C. Merlet-Benichou ◽  
J. P. Geloso
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Sesame Oil ◽  
Newborn Rats ◽  
Maternal Milk ◽  
Infant Rats

We previously demonstrated that in rats gastric acid secretion declines after birth and drops steeply on day 12 of life. In the present study, we investigated the part played in this decline by prostaglandin E2 (PGE2) from maternal milk. PGE2 content was first measured in the milk of untreated dams 0, 1, 5, 10, 12, 15, and 18 days after parturition. PGE2 levels were high during the first 5 days (123.5-200.5 pg/ml), declined significantly between days 10 and 15 (56.6-85.4 pg/ml; P less than 0.05), and dropped to 18.4 pg/ml on day 18. We also found that depleting milk of PGE2 prevented drop of acid secretion in 12-day-old suckling rats. Injecting lactating dams with indomethacin significantly reduced milk PGE2 content by 65% vs. milk of untreated dams. Surprisingly, administration of sesame oil, the indomethacin vehicle to the dams, increased milk PGE2 content by 182%. In the pups of the indomethacin-treated dams, acid secretion did not drop. On the contrary, in vivo basal and histamine-induced acid output rose markedly by 40 and 50%, respectively, and in vitro the net movements of 36Cl and 22Na measured in the isolated stomach indicated that active Cl- secretion had resumed. Mucosal PGE2 did not appear to be significantly involved in early development of acid secretion because administration of indomethacin to pups from untreated dams did not significantly modify the secretion measured on day 12. Data indicate that maternal milk depletion of PGE2 prevents the drop of gastric acid secretion previously observed in 12-day-old pups and suggest that in infant rats maternal PGE2 plays a physiological part in regulating acid secretion.

Canine gastric and pancreatic secretion during intestinal distension and intestinal perfusion with choline derivatives

1969 ◽  
Vol 47 (2) ◽  
pp. 115-118 ◽  
Author(s):  
P. T. Sum ◽  
H. L. Schipper ◽  
R. M. Preshaw
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Pancreatic Secretion ◽  
Intestinal Perfusion ◽  
Conscious Dogs ◽  
Balloon Distension ◽  
Acetylcholine Chloride ◽  
Intestinal Distension ◽  
External Pancreatic Secretion

Balloon distension of the duodenum in conscious dogs increased gastric acid secretion, but had no effect on external pancreatic secretion. Duodenal infusion of solutions of acetylcholine chloride did not stimulate pancreatic secretion. Duodenal infusion of solutions of bethanechol stimulated both gastric acid secretion and pancreatic secretion, but the same doses of bethanechol were more effective secretory stimulants when introduced intravenously.

scholarly journals Metabolism and gastric acid secretion. Substrate-dependency of aminopyrine accumulation in isolated rat parietal cells

1985 ◽  
Vol 227 (1) ◽  
pp. 223-229 ◽  
Author(s):  
G P Shaw ◽  
N G Anderson ◽  
P J Hanson
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cell ◽  
Parietal Cells ◽  
Intestinal Epithelial ◽  
Acid Secreting ◽  
High Concentrations ◽  
Isolated Rat

The substrate-dependency of gastric acid secretion was investigated in isolated rat parietal cells by using the accumulation of the weak base aminopyrine as an index of acid secretion. Exogenous substrates enhanced accumulation of aminopyrine in rat parietal cells stimulated by secretagogues, and this effect was probably directly related to the provision of energy for acid secretion. At physiological concentrations, certain of the substrates (glucose, oleate, lactate, D-3-hydroxybutyrate, L-isoleucine, L-valine and acetoacetate) could support acid secretion, with glucose being the most effective. L-Leucine and acetate were only effective stimulators of parietal-cell aminopyrine accumulation at high concentrations (5mM). L-Glutamine was unable to stimulate aminopyrine accumulation even at high concentrations, and glutaminase activity in parietal cells was estimated to be low by comparison with small-intestinal epithelial cells. Variation in the concentrations of D-3-hydroxybutyrate and L-isoleucine, but not of glucose, within the physiological range affected their ability to support aminopyrine accumulation. The presence of 5 mM-L-isoleucine, 5 mM-lactate and combinations of certain substrates at physiological concentrations produced aminopyrine accumulation in stimulated parietal cells that was greater than that obtained in cells incubated with 5 mM-glucose alone. In conclusion, fulfillment of the metabolic requirements of the acid-secreting parietal cell under physiological circumstances requires a combination of substrates, and integration of the results with previous data [Anderson & Hanson (1983) Biochem. J. 210, 451-455; 212, 875-879] suggests that after overnight starvation in vivo metabolism of glucose, D-3-hydroxybutyrate and L-isoleucine may be of particular importance.

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