[The pathways of taurine influences on gastric secretion].

In chronic experiments with dogs with gastric fistulas the influence of amino acid taurine on the gastric secretion was investigated. We showed that taurine did not cause acid gastric secretion out of digestion, but increased the gastric secretion stimulated by histamine, increased the contents of gastric acid and pepsine in gastric secretes. When administered either 15 minutes or two hours prior histamine injection, taurine affected the Na+ and K+ concentrations in gastric juice. The greatest changes in the basic indices of gastric secretion were observed 14 hours after administration of taurine. In these experiments the contents of total proteins and components of adenile system in gastric secretes was increased also. Blockade of cholinoreceptors by atropine, benzohexonium and IEM-1678 decreased the effects of taurine on gastric secretion stimulated by histamine. Blockade of a-adrenoreceptors by phentolamine did not prevent the taurine-induced effects on histamine-stimulated gastric secretion. It is established that under conditions of the blockade of beta-adrenoreceptors by obsidane, taurine does not manifest entirely its potentiating influence on the gastric secretion stimulating by histamine. The data obtained indicate that taurine affects gastric secretion stimulated by histamine and realization of this effect occurs through M- and N-cholino- and B-adrenoreceptors.

Bravo capsule system optimizes intragastric pH monitoring over prolonged time: effects of ghrelin on gastric acid and hormone secretion in the rat.

AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time. METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed. RESULTS: All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001). CONCLUSION: pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.

Gastrimmune-induced antigastrin-17 antibodies inhibit acid secretion in a rat fistula model.

BACKGROUND: Gastrimmune is an immunogenic form of gastrin. It raises in situ antibodies against two proliferative forms of gastrin: amidated and glycine-extended gastrin-17. It has been shown to have a therapeutic action in several in vivo tumour models. Following immunization, due to the complex equilibrium that exists between the antibodies and gastrin, it is not technically feasible to assay for free gastrin. AIM: To determine the effect of Gastrimmune-induced antigastrin antibodies on acid secretion. METHOD: A rat gastric fistula model was used. Animals (six per group) were immunized with a control immunogen or ascending doses of Gastrimmune. Acid output was measured following infusion of increasing doses of gastrin-17 and pentagastrin. RESULTS: Gastrimmune-induced antibodies significantly reduced gastrin-17-stimulated acid output compared to control animals (Gastrimmune at 200 microg/rat vs. control; acid output following 30 ng gastrin-17, 0.01 vs. 0.16, P < 0.001; following 120 ng gastrin-17, 0.022 vs. 0.29, P < 0.001). CONCLUSIONS: Gastrimmune significantly inhibits gastrin-17-stimulated acid output. This biological assay suggests that the antigastrin antibodies effectively bind gastrin-17. In addition to its use as an antineoplastic agent, Gastrimmune may have a role as an acid-decreasing agent in oesophagogastric pathology.

Selective action of a CCK-B/gastrin receptor antagonist, S-0509, on pentagastrin-, peptone meal- and beer-stimulated gastric acid secretion in dogs.

BACKGROUND: The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown. AIM: To evaluate the antisecretory effects of S-0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants. METHODS: Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer. RESULTS: In the Heidenhain pouch model, both intravenously administered and orally administered S-0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol-stimulated or histamine-stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non-selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S-0509 significantly inhibited pentagastrin-stimulated gastric acid secretion, yet the drug had no effect on carbachol-stimulated secretion. CONCLUSIONS: S-0509 is a selective CCK-B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin-releasing substances, but does not inhibit histamine-stimulated and carbachol-stimulated acid secretion.

Characterization of antisecretory and antiulcer activity of CR 2945, a new potent and selective gastrin/CCK(B) receptor antagonist.

The antigastrinic, antisecretory and antiulcer activities of CR 2945, (R)-1-naphthalenepropanoic acid,beta-[2-[[2-(8-azaspiro[4.5]dec-8-yl-carbonyl)-4,6-dimethylph enyl] amino]-2-oxoethyl], were investigated in vitro and in vivo in rats and cats. Its activities were compared with those of two gastrin/CCK(B) receptor antagonists, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)-N'-(3-methylphenyl)urea and CAM-1028 (4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[1,7,7-trimethylbicyclo [2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino -4-oxo-[1S-1alpha,2beta[S'(S')4alpha]]-butanoate -N-methyl-D-glucamine), of the histamine H2 receptor antagonist, ranitidine, and the proton pump inhibitor, omeprazole. Cytosolic Ca2+ elevation in rabbit parietal cells induced by gastrin (50 nM) was blocked by CR 2945 with an IC50 value of 5.9 nM. CAM-1028 and L-365,260 showed similar activity. CR 2945 antagonized pentagastrin-stimulated gastric acid secretion in rats (ED50 = 1.3 mg kg(-1) i.v. and 2.7 mg kg(-1) i.d.) and cats (1.6 mg kg(-1) i.v.). CR 2945 was slightly less potent than the reference compounds after i.v. administration, whereas after intraduodenal (i.d.) administration, it was more potent than both ranitidine and omeprazole. In the rat, the gastrin antagonism exhibited by CR 2945 was reversible and competitive, with a pA2 value of 7.33. CR 2945 had specific antigastrin activity, as it was unable to antagonize the gastric acid secretion stimulated by histamine or carbachol in rats up to the dose of 30 mg kg(-1). CR 2945 was about as efficacious as ranitidine against the indomethacin- and ethanol-induced gastric ulcers and the cysteamine-induced duodenal ulcer in rats. On the contrary, L-365,260 was only slightly effective. These results suggest that CR 2945 might be a promising compound for the therapy of acid-related disorders, and that its clinical use could help clarify the therapeutic potential of gastrin/CCK(B) receptor antagonists in the gut.

YM022, a highly potent and selective CCKB antagonist inhibiting gastric acid secretion in the rat, the cat and isolated rabbit glands.

We investigated the effects of the novel CCKB/gastrin antagonist YM022 on gastric acid secretion in vivo and in vitro, compared to CI-988 and L365,260 as reference antagonists. In the anaesthetized rat, pentagastrin-induced stimulation of gastric acid secretion was dose-dependently and up to 100% inhibited by i.v. administration of YM022 with an ID50 of 0.009 +/- 0.0006 mumol/kg h in comparison to 0.6 +/- 0.03 and 3.40 +/- 0.05 mumol/kg h for CI-988 and L-365,260, respectively. In the gastric fistula cat, i.v. administration of YM022 produced a similar inhibitory effect with an ID50 of 0.02 mumol/kg in comparison to 1.6 and 2.5 mumol/kg for CI-988 and L-365,260, respectively. Furthermore, bolus injection of 0.6 mumol/kg YM022 produced 100% inhibition within 30 min and 85% inhibition was still observed after 3 h. In the isolated rabbit gastric glands, CCK8-stimulated 14C-aminopyrine uptake was inhibited according to the following rank order of potency: YM022 (IC50 = 0.0012 microM) > > CI-988 (IC50 = 0.2 microM) > > L365,260 (IC50 = 2.8 microM). Unlike with L365,260, no influence of CI-988 and YM022 on histamine-stimulated acid output was shown in this study. Thus, YM022 is a highly potent and selective gastric CCKB/gastrin receptor antagonist and has a long-lasting inhibitory effect on gastric acid secretion.

Sustained cholecystokinin-B/gastrin receptor blockade does not impair basal or histamine-stimulated acid secretion in chronic gastric fistula rats.

Gastrin is a physiologically important secretagogue. It is thought to stimulate parietal cells indirectly by mobilizing histamine from enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin stimulates the secretory activity and growth of the ECL cells via an action on cholecystokinin-B/gastrin receptors. Acute cholecystokinin-B/gastrin receptor blockade is known to inhibit gastrin-stimulated acid secretion but whether sustained cholecystokinin-B/gastrin receptor blockade will impair basal, gastrin- and histamine-stimulated acid secretion remains uncertain. The present study was designed to study the effect of long-term (4 weeks) cholecystokinin-B/gastrin receptor blockade on basal and stimulated acid secretion in conscious rats. The selective cholecystokinin-B/gastrin receptor antagonist YM022 (3 mumol.kg-1.hr-1) was given to gastric fistula rats by continuous subcutaneous infusion via osmotic minipumps for various times from 2 hr to 4 weeks. Basal, gastrin- and histamine-stimulated acid secretion were examined during and after cessation of treatment. Basal and histamine-stimulated acid secretion was not affected by YM022 during the 4 week period of administration, whereas gastrin-induced acid secretion was inhibited. YM022 induced hypergastrinaemia in freely fed rats but did not affect the serum gastrin level in fasted rats. The serum gastrin concentration and gastrin-induced acid secretion returned to control levels 3-7 days after termination of YM022 administration.

Comparative evaluation of the role of endogenous gastrin in basal acid secretion in conscious rats provided with chronic fistula and pylorus ligation.

We determined the relative contributions of endogenous gastrin, histamine and cholinergic tone to basal acid secretion in chronic fistula rats. Results were compared with those for acid secretion in pylorus-ligated rats. In chronic fistula rats, YM022 ¿(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1 H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea¿ dose-dependently inhibited pentagastrin-stimulated acid secretion and abolished this secretion at 1 mumol/kg, s.c., but did not affect histamine- and carbachol-induced acid secretion even at 10 mumol/kg. In contrast, famotidine at 1 mumol/kg completely inhibited not only the acid secretion induced by histamine but also those by pentagastrin and carbachol. Furthermore, atropine abolished carbachol- and pentagastrin-stimulated acid secretion and significantly suppressed histamine-stimulated acid secretion at 0.1 mumol/kg. YM022 dose-dependently inhibited basal acid secretion. The YM022 dosage required to inhibit basal acid secretion is consistent with that required to suppress pentagastrin-induced acid secretion. Famotidine (1 mumol/kg) and atropine (0.1 mumol/kg) also abolished basal acid secretion. In pylorus-ligated rats, YM022 inhibited acid secretion in a dose-dependent manner; the inhibition at 1 mumol/kg, i.v. was 65%. No additional effect was observed when rats were dosed at 30 mumol/kg. Famotidine partially inhibited acid secretion in these rats, whereas atropine abolished this secretion. These results indicate that the major part of basal acid secretion in rats is attributable to endogenous gastrin via histamine- and cholinergic tone-dependent pathways. Moreover, pylorus ligation reduces the relative contribution of gastrin to acid secretion due to the activation of cholinergic tone.

Effects of anaesthetic agents on basal and histamine-stimulated acid secretion in the fistula rat.

OBJECTIVES: Anaesthetized rats or surgically modified preparations such as the Shay rat are widely used to study upper gastrointestinal function in the laboratory. Despite the existence of reports demonstrating that agents such as barbiturates can influence acid output, a systematic study of the effects of anaesthetics on gastric secretion has not been undertaken. METHODS: Basal and histamine-stimulated acid output were measured in chronic fistula rats after administration of injectable and volatile anaesthetics frequently used in studies of gastric secretion in anaesthetized animals. With the exception of ether, for which recovery is very rapid, sedating rather than full anaesthetic doses were used. RESULTS: Chloralose (40 mg/kg) had no significant effect on gastric secretion. Pentobarbitone (25 mg/kg) inhibited basal and histamine-stimulated acid output, but the effect was relatively short-lived and secretion returned to control levels after 2 h. Urethane (750 mg/kg) markedly inhibited basal acid output and abolished the secretory response to histamine given 15 to 60 min later. The effects of urethane on acid secretion persisted for the entire 3 h duration of experiments, during which time basal acid output declined to levels observed in fully anaesthetized rats given 1.5 g/kg. Full anaesthesia with ether for 60 min also caused profound inhibition of basal secretion and, like urethane, abolished the effect of histamine despite the fact that the animals recovered consciousness within 5 min. CONCLUSIONS: The differential activity of anaesthetics and profound antisecretory activity of ether and urethane should be taken into account when studying gastrointestinal function and mucosal ulceration in anaesthetized animals.

Activity of the new histamine H2-receptor antagonist zolantidine at cardiac and gastric H2-receptors.

The effect of the new histamine H2-receptor antagonist zolantidine was studied in different cardiac and gastric H2-receptor assays in comparison with ranitidine. Zolantidine (0.1-10 mumol/l) competitively antagonized the positive effects of histamine in the spontaneously beating guinea pig atria and in the electrically stimulated guinea pig papillary muscle (pA2 values were 6.98 and 6.78, respectively). At the highest concentrations zolantidine also reduced basal heart rate and cardiac contractility. In the isolated rat gastric fundus zolantidine up to 100 mumol/l did not modify histamine-induced acid secretion; it was similarly ineffective against dimaprit-induced acid secretion in the gastric fistula of conscious cats (up to 3 mumol/kg i.v.) and against histamine in the anesthetized rat with lumen-perfused stomach (up to 30 mumol/kg i.v.). In all these gastric secretory models ranitidine, as expected, antagonized histamine H2-receptor-mediated responses, showing a potency comparable to that found in cardiac preparations (pA2 values were 6.84, 6.38 and 6.78 in the atria, papillary muscle and gastric fundus, respectively). These data clearly showed that zolantidine is a very peculiar histamine H2-receptor antagonist, capable of distinguishing between cardiac and gastric H2-receptors; however, it still has to be elucidated whether this depends on a true heterogeneity in the histamine H2-receptor population or on the physicochemical properties of the drug.

Intracerebroventricular neuropeptide Y increases gastric and pancreatic secretion in the dog.

BACKGROUND: Neuropeptide Y (NPY), a centrally located neurotransmitter, is known to increase appetite in fasted and satiated animals. In addition to evaluating NPY's effect on eating behavior, this study was intended to determine whether intracerebroventricular (ICV) NPY would have an effect on canine gastric and pancreatic secretion. METHODS: Four dogs were prepared with cerebroventricular guides and gastric and pancreatic fistulas. ICV and intravenous NPY was administered during intragastric titration of a glucose and peptone meal. During this study, gastric and pancreatic secretion was measured, as well as insulin levels and pancreatic polypeptide (PP). An additional set of four dogs were prepared with esophageal fistulas and cerebroventricular guides, and the effect of ICV NPY on sham feeding was studied. RESULTS: ICV NPY significantly increased sham feeding, meal-stimulated gastric and pancreatic secretion, basal gastric acid, pancreatic bicarbonate, insulin levels, and PP. Vagotomy blocked the effect of ICV NPY on gastric acid secretion in a urethane-anesthetized rat model with acute gastric fistula. CONCLUSIONS: ICV NPY increased sham feeding, gastric and pancreatic secretion, insulin levels, and PP in the dogs. NPY's effect on gastric secretion was blocked by vagotomy in a rat model. NPY should be considered a candidate mediator of cephalic phase secretion.

[Effect of glutamate and combined with inosine monophosphate on gastric secretion]. / Deistvie glutamata i ego sochetaniia s inozinmonofosfatom na zheludochnuiu sekretsiiu.

Experiments on dogs with Pavlov pouch and gastric fistula demonstrate that monosodium glutamate (MSG) enriched with inosine monophosphate (IMP) potentiate pentagastrin-induced gastric secretion. The preparation (Chi-Mi) was introduced directly into the intestine through a fistula. When given alone in an equal quantity MSG produced the same effect. In per os administration Chi-Mi was more effective, probably due to a different response of the gustatory receptors to MSG and Chi-Mi. When the latter two were added to meat used as a food stimulus, Chi-Mi brought about more intensive gastric secretion in all its phases. In sham feeding Chi-Mi also intensified the secretion augmenting the reflex phase of gastric secretion when added to food substances. The findings may appear helpful in further search for medical application of glutamate and allied substances.

Parenteral and enteral nutrition and the enterocutaneous fistula treatment. I. Investigations on fistula output, nutritional status complications.

Prospective evaluation were made of 45 patients with postoperative small bowel fistulas treated with total parenteral nutrition (TPN) and enteral nutrition (EN) between 1971-1988. The administration of TPN in the early treatment of enteric fistulas decreased the mean fistula output significantly (p < 0.05-0.001) and provided an effective tool in the control of high-output fistulas. The electrolyte contents of different fistula secretions were unchanged and the losses through the fistulas depended on the daily output. In patients with high-output fistulas acid-base balance disturbances had to be corrected. When comparing two parenteral nutrition regimens (carbohydrate+amino acids /CH + AA/ versus carbohydrate + amino acids + fat /CH + AA + F/) both facilitated the reduction of fistula secretion (in high-output fistulas. CH + AA = -50.2%; CH + AA + F = -49%). Positive nitrogen balance was achieved in non septic patients after 13 days of treatment. Improvement of serum protein and albumin occurred by the time of fistula healing. In non surviving patients significant decrease in protein synthesis was observed. Out 7 of 75 central venous catheters yielded positive bacterial cultures (9.3%). In 5 patients autopsy proved generalized sepsis. The use of parenteral and enteral nutrition proved to be a powerful method for controlling the enterocutaneous fistulas and maintaining the nutritional integrity of patients.

Fat inhibits pentagastrin-stimulated acid secretion from the duodenum but not from the proximal jejunum in chronic gastric fistula rats.

The effect of fat emulsion in the upper intestine on the maximal gastric acid response to pentagastrin was studied in chronic gastric fistula (GF) rats with a 4-cm blind loop of the duodenum anastomosed to the jejunum (Roux-en-Y). Fat emulsion in the loop inhibited the acid response by 85%. To localize the site of the inhibitory mechanism, GF rats were provided with Thirty-Vella loops of the duodenum (bile and pancreatic ducts transplanted to the proximal jejunum) or with Thirty-Vella loops of the proximal jejunum and a Roux-en-Y loop of the duodenum to prevent gastric juice from entering the duodenum. Perfusion of the duodenal loop with fat emulsion mixed with bile and pancreatic juice reduced the acid response by 49%, but perfusion of the proximal jejunal loop did not alter the response. It is concluded that the intestinal mechanism for inhibition of acid secretion by fat is located in the duodenum in rats.

Antisecretory activity of omeprazole in the conscious gastric fistula cat: comparison with famotidine.

The antisecretory activity of the H+/K+ ATPase inhibitor omeprazole was studied in the conscious gastric fistula cat in comparison with the H2-blocker famotidine. Omeprazole caused a dose-dependent inhibition of the dimaprit-induced acid secretion, being approximately fivefold less potent than famotidine (intravenous ID50S were 0.34 +/- 0.03 and 0.067 +/- 0.015 mumol/kg for omeprazole and famotidine, respectively). Omeprazole caused a non-competitive inhibition of the dose-response curve to dimaprit, whereas famotidine induced a parallel shift to the right without depressing the maximum response. Conversely from famotidine, the antisecretory effect of omeprazole was found to be dependent on the acid secretory state of the stomach, the effect being more evident when the compound was administered at the plateau of acid secretion. The inhibitory effect of omeprazole was very long lasting (25% inhibition was still present 24 h after administration of the drug) whereas that of famotidine was overcome by dimaprit infusion within 3-4 h. The antisecretory effect of omeprazole concerned to the same extent the volume and the acid concentration of the gastric juice, whereas famotidine reduced mainly the volume. When the stimulus was represented by pentagastrin the intravenous ID50 values were 0.57 +/- 0.03 and 0.088 +/- 0.015 mumol/kg for omeprazole and famotidine. respectively. From the above data it may be concluded that the antisecretory profile of omeprazole differed markedly from that of famotidine, independently from the potency and the efficacy of the two drugs.

Studies on neurotensin. II. Release of neurotensin.

The objective of these experiments was to confirm the localization of neurotensin (NT) in gut endocrine cells of the canine small intestine using immunohistochemistry. In addition, the release of NT from the canine small intestine in response to selective perfusion of a fatty acid (oleate), triglyceride (Lipomul) or products of fat digestion into various segments of the small intestine was studied. In the immunohistochemical study, NT was found to be primarily localized in true endocrine cells of the ileal mucosa. In addition, NT was not found or only negligible numbers of cells were seen outside the lower small intestine. This observation supports previous results based on radioimmunoassay and immunohistochemistry studies. Based on these morphological findings, NT would be released by luminal secretagogues, of which fat appears to be the most potent. In the selective perfusion studies, perfusion of oleic acid into the jejunum of the chronic dog caused NT release, whereas perfusion of the ileum in which NT cells were most abundant was ineffective. This observation suggests that a neural or endocrine message is released to the ileal NT cell from the jejunum, causing NT release. This series of studies was carried out to elucidate the mechanism of NT release and to find the direct luminal stimulants of NT by using both chronic and acute experimental models. These studies suggest that NT is not significantly released under anesthesia and that undigested fat, like triglyceride, does not release NT in either the upper or lower small intestine. Furthermore, digested fat, like oleate or digestive juices in the lower small intestine, is not a direct stimulant of NT release.

Peptide YY inhibits the insulinotropic action of gastric inhibitory polypeptide.

Peptide YY (PYY) is released from the gut after ingestion of fat or after a meal. The purpose of this investigation was to examine the effect of PYY on gastric inhibitory polypeptide (GIP)-stimulated insulin release in conscious dogs with gastric and duodenal fistulas. In control experiments, 6 dogs received GIP (400 pmol/kg, i.v., for 1 h) and glucose (0.6 g/kg, i.v., for 1 h); the integrated insulin response over a 1-h period was 142 +/- 32.7 ng-60 min/ml. The plasma GIP levels achieved by this procedure were similar to those observed by intraduodenal infusion of Lipomul (2 ml/min), suggesting that the dose of GIP used was within the physiologic range. Intravenous infusion of three different doses of PYY (100, 200, or 400 pmol/kg.h) caused a significant inhibition of insulin release stimulated by GIP + glucose; the integrated insulin response was reduced to 105, 88, and 79 ng-60 min/ml, respectively. On the other hand, PYY (400 pmol/kg.h) had no effect on insulin secretion induced by intravenous glucose (0.6 g/kg.h) alone. These results indicate that PYY specifically inhibits the insulinotropic action of GIP and that PYY may play a negative-feedback regulatory role in the enteroinsular axis.

Effect of aging on gastric acid secretion, serum gastrin, and antral gastrin content in rats.

The purpose of this study was to characterize the effects of aging on gastric acid secretion and on serum and antral concentrations of gastrin in rats. Young and old Fischer 344 rats were prepared with gastric fistulas. Twenty-four hours after surgery, graded doses of human synthetic gastrin-17 (SHG-17) (2, 5, 10, 20, and 40 micrograms/kg) were given intravenously in random order. Gastric secretions were collected for gastric acid measurement before and at 15-min intervals after each dose of gastrin. In a separate study, blood was collected and the stomachs were removed for antral gastrin extraction from fed young and old rats. Serum and antral gastrin was measured by radioimmunoassay. The basal and gastrin-stimulated acid secretions were significantly decreased in aged rats compared to the young rats. The basal acid output was 0.4 +/- 0.2 microeq/15 min in the aged rats and 1.5 +/- 0.5 microeq/15 min in the young. The maximal acid output stimulated by gastrin was 11.1 +/- 1.8 microeq/15 min in the aged rats and 24.2 +/- 2.8 microeq/15 min in the young. Both serum and antral concentrations of gastrin were significantly decreased in aged rats. Serum gastrin concentration was 114.8 +/- 7.4 pg/ml in the aged rats and 192.0 +/- 14.4 pg/ml in the young. Antral gastrin concentration was 3.9 +/- 0.5 micrograms/g tissue in the aged rats, which was significantly less than the concentration in the young (6.5 +/- 0.4 micrograms/g tissue). Antral gastrin content did not change with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of a new prostaglandin E2 analogue (FCE 20700) on gastric acid and pepsin secretion in the dog.

The effects of FCE 20700, a new prostaglandin E2 analogue, on gastric acid and pepsin secretion stimulated by different secretagogues were studied in dogs. Intravenous FCE 20700 produced a significant inhibition of total acid output (TAO) induced by pentagastrin or histamine in gastric fistula (GF) dogs. This effect was short-lasting and mainly due to a reduction in the volume of gastric juice with little acid concentration change. TAO and pepsin output stimulated by 2-deoxy-D-glucose were similarly inhibited by intravenous FCE 20700. In dogs chronically fitted with both GF and Heidenhain pouch (HP), intragastric FCE 20700 significantly inhibited TAO stimulated by pentagastrin or histamine from HP, while acid secretion from GF was not significantly affected. It is concluded that FCE 20700 possesses a weak antisecretory activity in dogs. Consequently the antiulcer effects of this prostaglandin derivative seem to be largely independent from its influence on gastric acid and pepsin secretion.