Gastric Acid Secretion In Dogs Research Articles

Preliminary comparative serological evaluation of Histamine H2 receptors in dogs with an acute onset of vomiting treated with Ranitidine and healthy dogs

Despite the lack of evidence of the ability to suppress gastric acid secretion in dogs, ranitidine (RT) is often used to control clinical signs in dogs with acute vomiting even if the way it happens it is still largely unknown. The aim of this study was thus to evaluate the therapeutic effect of ranitidine on H2 receptors in dogs with acute vomiting. To investigate the RT activity a preliminary study was performed in dogs which underwent gastroscopy analyses, demonstrating that the level of H2R observed in the serum and gastric wall tissue was the same [1.473(1.30; 1.79) ng/ml and 1.498 (1.33; 1.85) ng/ml, respectively]. After that H2R levels in the serum of 22 healthy dogs (Group 1) and in a group of 22 dogs with acute vomiting (Group 2) were compared both before (T0), after 7–10 days (T1) of 2 mg/kg twice a day ranitidine administration and after 11 days since the drug was discontinued (T2). Significant differences (p<0.001) were detected between the level of circulating H2R among Group 1: 0.41 ng/ml (0.28;0.54) and Group 2: 2.27 ng/ml (2.11;2.49) at T0. In Group 2, no difference in the level of H2R was detected in samples collected at T0 compared to those at T1 [T1: 2.32 ng/ml (2.14; 2.49)] and T2 [T2: 2.30 ng/ml (1.99;2.69)]. In Group 2 all patients but one displayed remission of symptoms attributable to inflammatory gastropathy at the first withdrawal (T1: 7–10 days), while at the second withdrawal (T2: after 21 days), remission was detected in all dogs. Our preliminary hypothesis is that the clinical efficacy of ranitidine is related to the greater expression of H2 receptors in patients with acute vomiting. This increased expression may be due to continuous pathological stimulus at the gastric level. Further studies with a wider population are needed to better investigate the activity of RT in dogs with acute onset of vomiting.

Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility.

Tegoprazan [(S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB), is a novel potent and highly selective inhibitor of gastric H+/K+-ATPase. Tegoprazan inhibited porcine, canine, and human H+/K+-ATPases in vitro with IC50 values ranging from 0.29 to 0.52 μM, while that for canine kidney Na+/K+-ATPase was more than 100 μM. A kinetic analysis revealed that tegoprazan inhibited H+/K+-ATPase in a potassium-competitive manner and the binding was reversible. Oral single administrations of tegoprazan ranging from 0.3 to 30 mg/kg in dogs were well absorbed into the blood stream and distributed in gastric tissue/fluid higher than in plasma. Tegoprazan potently inhibited histamine-induced gastric acid secretion in dogs, and a complete inhibition was observed at 1.0 mg/kg starting from 1 hour after administration. Moreover, an oral administration of tegoprazan at 1 and 3 mg/kg reversed the pentagastrin-induced acidified gastric pH to the neutral range. Interestingly, 3 mg/kg tegoprazan immediately evoked a gastric phase III contraction of the migrating motor complex in pentagastrin-treated dogs and similar effects was observed with the other P-CAB, vonoprazan. Tegoprazan is the novel P-CAB that may provide a new option for the therapy of gastric acid-related and motility-impaired diseases.

The long-lasting effect of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion in dogs.

We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2-{[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl}-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of TU-199 using a measurement of intragastric pH for 24 h in gastric fistula dogs whose gastric acid secretion was stimulated by histamine. Single oral administration of TU-199 (0.1, 0.2 and 0.4mgkg(-1)) dose-dependently suppressed gastric acid secretion stimulated by histamine infusion. Oral treatment with TU-199 (0.2, 0.4 and 0.8 mg kg(-1)) also dose-dependently inhibited acid secretion induced by carbachol and tetragastrin. The inhibitory effect of TU-199 on stimulated gastric acid secretion was more potent than that of omeprazole, a well-known H+,K(+)-ATPase inhibitor in dogs. Repeated oral treatment with TU-199 at a dose of 0.2 mg kg(-1) once a day for seven days markedly suppressed histamine-stimulated gastric acid secretion in dogs. This inhibitory effect of TU-199 reached a maximum level after three or four doses and was more pronounced than that of omeprazole or lansoprazole. In gastric fistula dogs, the duration of intragastric pH-elevation by administration of TU-199 (0.3 mg kg(-1)) was much longer than that of omeprazole (0.6mgkg(-1)) or lansoprazole (0.9mgkg(-1)). The IC50 values (doses resulting in 50% inhibition) of TU-199, omeprazole and lansoprazole with regard to H+,K(+)-ATPase activity in dog gastric mucosal microsomes were 8.6, 8.8 and 9.9 microM, respectively. These results indicate that TU-199 inhibits gastric acid secretion via suppression of a H+,K(+)-ATPase activity. Our findings also suggest that TU-199 might have potent and long-lasting effects on gastric acid secretion.

Biology of Incretins: GLP-1 and GIP

This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The published literature was reviewed, with emphasis on recent advances in our understanding of the biology of GIP and GLP-1. GIP and GLP-1 are both secreted within minutes of nutrient ingestion and facilitate the rapid disposal of ingested nutrients. Both peptides share common actions on islet beta-cells acting through structurally distinct yet related receptors. Incretin-receptor activation leads to glucose-dependent insulin secretion, induction of beta-cell proliferation, and enhanced resistance to apoptosis. GIP also promotes energy storage via direct actions on adipose tissue, and enhances bone formation via stimulation of osteoblast proliferation and inhibition of apoptosis. In contrast, GLP-1 exerts glucoregulatory actions via slowing of gastric emptying and glucose-dependent inhibition of glucagon secretion. GLP-1 also promotes satiety and sustained GLP-1-receptor activation is associated with weight loss in both preclinical and clinical studies. The rapid degradation of both GIP and GLP-1 by the enzyme dipeptidyl peptidase-4 has led to the development of degradation-resistant GLP-1-receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. These agents decrease hemoglobin A1c (HbA1c) safely without weight gain in subjects with type 2 diabetes. GLP-1 and GIP integrate nutrient-derived signals to control food intake, energy absorption, and assimilation. Recently approved therapeutic agents based on potentiation of incretin action provide new physiologically based approaches for the treatment of type 2 diabetes.

The effect of the antihistamines on the antral phase of gastric acid secretion in dogs.

Journal Article The effect of the antihistamines on the antral phase of gastric acid secretion in dogs Get access R A Payne, R A Payne The University Department of Surgery, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar F D Naylor, F D Naylor The University Department of Surgery, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar A W Kay A W Kay The University Department of Surgery, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 48, Issue 212, May 1961, Pages 683–686, https://doi.org/10.1002/bjs.18004821222 Published: 06 December 2005

Efficacy of Omeprazole for the Prevention of Exercise-Induced Gastritis in Racing Alaskan Sled Dogs

Exercise-induced gastritis and gastric ulcers are common in humans and horses, and recently have been described in racing sled dogs. The cause of exercise-induced gastric disease is not completely understood in any species, but pharmacologic suppression of acid secretion is an effective treatment in humans and horses. Thus, we tested the hypothesis that omeprazole, a proton-pump inhibitor shown to reduce gastric acid secretion in dogs, would reduce the severity of exercise-induced gastric disease. Three teams of 16 dogs each competing in the 2002 Iditarod Sled Dog Race were recruited for participation. Within each team, dogs were randomly assigned to either treatment (20 mg omeprazole PO q24h) or placebo. Treatments were administered until either completion of the race or withdrawal of an individual dog from competition. Gastric endoscopy was performed in all dogs 24 hours after completion or withdrawal, and the gastric mucosa was scored by using a subjective severity score (0 = normal, 3 = numerous bleeding ulcers). Treatment with omeprazole significantly reduced mean gastric severity score compared to placebo (omeprazole: 0.65 ± 0.17, placebo: 1.09 ± 0.18; P= .028), but also was associated with increased frequency of diarrhea during the race (omeprazole 54%, placebo 21%; P= .017). Examination of our data suggests that omeprazole may be an effective treatment for exercise-induced gastric disease in racing sled dogs. However, further investigation regarding the cause and clinical relevance of diarrhea associated with omeprazole treatment must be conducted before omeprazole can be recommended for routine prophylactic treatment in these athletes.

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs

Wine apparently stimulates gastric acid secretion both in man and animals, yet the underlying mechanism remains unclear. The present study was attempted to clarify the pharmacological properties involved in gastric acid secretion stimulated by wine in beagle dogs. Commercially available red or white wine, 14% ethanol, or 10% peptone meal was intragastrically administered to dogs with vagally denervated Heidenhain pouches. Gastric acid secretion was stimulated by both red and white wines (25–50 ml) for 45–60 min. While S-0509 only tended to inhibit wine-stimulated gastric acid secretion, both atropine and famotidine significantly inhibited wine-stimulated gastric acid secretion. Plasma gastrin level was not significantly increased by administration of red and white wines. Administration of 14% ethanol also stimulated gastric acid secretion, but the effect was about half of that of wine. Combined administration of wine and peptone resulted in a biphasic stimulation of gastric acid secretion. S-0509, atropine and famotidine significantly inhibited wine+peptone meal stimulation, yet the order of inhibition of cumulative acid secretion was in the order, famotidine>atropine>S-0509. It was concluded that wine stimulated gastric acid secretion in denervated dogs via acethylcholine- and histamine-dependent mechanisms, but nearly independent from the intervention of gastrin.

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

The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown. 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. 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. 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. 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.

Mechanism by which beer and wine stimulates gastric acid secretion in dogs: Role of gastrin

Mechanism by which beer and wine stimulates gastric acid secretion in dogs: Role of gastrin

Gastric acid secretion in dogs in response to combinations of beer, ethanol and peptone meal--the role of endogenous gastrin.

To examine the effects of beer, ethanol, peptone meal and combinations of either peptone meal and beer or peptone meal and ethanol on gastric acid secretion in vagally denervated pouch dogs. The oral administration of either 200 mL of beer, 5% ethanol or 10% peptone meal significantly stimulated gastric acid secretion for 60-90 min in these dogs. With 5% ethanol the plasma gastrin concentration was not affected for 90 min. Combinations of 10% peptone and beer (peptone-beer) or 10% peptone and 5% ethanol (peptone-ethanol) potentiated the acid secretion and increased the plasma gastrin level. While a selective cholecystokinin-B/gastrin receptor antagonist, S-0509, had no effect on ethanol-stimulated acid secretion, the compound markedly inhibited both peptone-beer-stimulated and peptone-ethanol-stimulated gastric acid secretion. Famotidine and atropine significantly inhibited gastric acid secretion stimulated by 5% ethanol, peptone-beer and peptone-ethanol. The mechanisms by which peptone-beer and peptone-ethanol stimulate gastric acid secretion may be mediated not only by increased plasma gastrin, but also by the action of histamine and acetylcholine coupled with the increased plasma gastrin. Ethanol-stimulated secretion appears to be unrelated to circulating gastrin, yet may be related to the acid regulatory mechanism involving histamine and acetylcholine.

P–338 - Effects of TU-199, a H+ K+-ATPase inhibitor, on gastric acid secretion in dogs

P–338 - Effects of TU-199, a H+ K+-ATPase inhibitor, on gastric acid secretion in dogs

Inhibition of sham feeding-stimulated acid secretion in dogs by immunoneutralization of gastrin.

A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs with esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes later, acid secretion was stimulated first by sham feeding for 5 min, then, 60 min later, by an intravenous infusion of a maximum stimulatory dose of histamine (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60 min. Acid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin-stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h-1) restored sham feeding-stimulated acid output blocked by administration of MAb 28.2, although the intrinsic acid response to sham feeding could not be seen with the background pentagastrin infusion. Furthermore, the plasma gastrin response to sham feeding was not blocked by atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sham feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs.

YF476 is a new potent and selective gastrin/cholecystokinin‐B receptor antagonist in vitro and in vivo

We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1, 4benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo. We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs. YF476 replaced the specific binding of [125I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with Ki values of 0.068, 0.62 and 0.19 nM, respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED50 value of 0.0086 micromol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 micromol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED50 values of 0.018 and 0.020 micromol/kg, respectively, but did not affect histamine-induced acid secretion. These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.

Inhibition of acid secretion by electrical acupuncture is mediated via beta-endorphin and somatostatin.

Electroacupuncture (EAP) was shown to inhibit basal gastric acid secretion in dogs and sham feeding-stimulated acid secretion in humans. However, its effect on a meal-stimulated acid secretion in dogs and the mechanisms involved remain unclear. In five dogs prepared with gastric cannulas, gastric acid secretion was determined by a dye-dilution technique for 60 min after intragastric administration of 200 ml of 4% mixed amino acid meal in six different experiments: study 1, no acupuncture; study 2, sham acupuncture (SAP); study 3, EAP; study 4, EAP plus naloxone; study 5, naloxone alone; and study 6, intravenous infusion of somatostatin (SS) and vasoactive intestinal peptide (VIP) at doses of 0.5 and 1.0 micrograms.kg-1.h-1, respectively. EAP was performed on three different points including Pishu, ZusanLi, and Neiguan. Biphasic electrical pulse (25-100 Hz, 12-16 mA) was applied continuously via needles for 75 min starting 15 min before meal. SAP on nonacupoints in hind- and forelegs was performed with the same electrical pulse. Plasma SS, VIP, beta-endorphin, and gastrin were determined by specific radioimmunoassays. EAP significantly inhibited acid secretion (75%; P < 0.01), which coincided with significant increases in plasma SS, VIP, and beta-endorphin and a significant decrease in plasma gastrin. Naloxone completely reversed EAP-induced inhibition of acid secretion and changes in plasma concentration of peptides. SAP also significantly suppressed acid output (30%; P < 0.05), with a modest but significant increase in plasma beta-endorphin. However, the inhibition by EAP on the acid output was significantly greater than that by SAP (P < 0.01). Furthermore, exogenous SS (0.5 microgram.kg-1.h-1) significantly inhibited acid output (78%), whereas VIP failed to inhibit gastric acid secretion. We conclude that, in dogs, EAP significantly inhibits meal-stimulated acid secretion. This acid inhibition is mediated by the release of beta-endorphin and somatostatin, and an endogenous opiate or opiates appear to play an important role in the release of SS, VIP, and beta-endorphin.

Modulation of pentagastrin-induced histamine release by histamine H3 receptors in the dog.

The histamine H3 receptor has been shown to inhibit pentagastrin-induced gastric acid secretion in dogs. Since pentagastrin releases histamine in dogs, we have now assessed whether the effects of H3-receptor ligands may be indirectly mediated by changes in gastric histamine release. Pentagastrin infusions (1 or 6 micrograms/kg/h), alone or together with the H3-receptor agonist (R) alpha-methylhistamine (1.2 mumol/kg/h) or the antagonist thioperamide (0.1 mumol/kg/h), were performed in dogs. One group (anaesthetized) was used for enzyme immunoassays of plasma histamine and, when required. (R) alpha-methylhistamine in the gastrosplenic vein, and another group (non-anaesthetized) for measurement of gastric acid secretion. Histamine levels were increased five- and eight-fold after 1 and 6 micrograms/kg/h pentagastrin, respectively, whereas acid output was nearly maximal at the lower dosage. (R) alpha-methylhistamine, at a plasma concentration of 0.15 microM, inhibited histamine release by 78% (P < 0.007) and 37% (not significant) and the total acid output by 44% (P < 0.05) and 19% (not significant) after infusion of 1 and 6 micrograms/kg/h pentagastrin, respectively. Thioperamide, together with pentagastrin in low dose, significantly increased histamine release by 212% (P < 0.05), whereas acid output increased by 34% (not significant). The histamine H3 receptor mediates a negative feedback control of pentagastrin-induced release of gastric histamine. It is tonically activated by endogenous histamine after pentagastrin in low dosage. The control of acid secretion by the H3 receptor seems to involve modulation of endogenous histamine release, possibly by means of enterochromaffin-like cells.

Antisecretory Effect of Leminoprazole on Histamine-Stimulated Gastric Acid Secretion in Dogs: Potent Local Effect

Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for >26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8–10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.

Neuropeptide Y functions as a physiologic regulator of cephalic phase acid secretion

Neuropeptide Y (NPY) has been established as a potent orexigenic peptide, and recent studies suggest that NPY stimulates cephalic phase secretion as well. However, it is not known whether NPY's effects are pharmacologic or physiologic. In order to determine the physiologic significance of NPY, we examined the effects of two putative NPY receptor antagonists, PYX-1 and PYX-2, on sham feeding and gastric acid secretion in dogs. Our results demonstrate that intracerebroventricular (i.c.v.) injection of PYX-1 and PYX-2 at 1000 pmol/kg doses significantly suppresses the gastric acid response to sham feeding in dogs. The volumes sham fed were not significantly altered with i.c.v. administration of the antagonists. Peripheral administration did not affect acid secretion nor sham feeding volumes. Our data suggest that central administration of the novel NPY antagonists, PYX-1 and PYX-2, results in significant suppression of acid secretion in dogs. This supports our hypothesis that NPY functions as a physiologic modulator of cephalic phase acid secretion.

Intracerebroventricular neuropeptide Y increases gastric acid secretion by decreasing tonic adrenergic inhibition of acid in dogs

Neuropeptide Y (NPY) has been shown to increase basal gastric acid secretion in dogs. We examined the hypothesis that NPY might increase gastric acid secretion by interaction with central catecholaminergic control of acid secretion in dogs. Studies were performed in awake canines with gastric fistulas and cerebroventricular guides which allowed injection into the lateral cerebral ventricle. Intracerebroventricular (i.c.v.) injection of yohimbine (5 μg/kg) increased acid secretion compared to control (yohimbine: 9.1 ± 3.3mmol//h;control: 1.8 ± 1.0mmol/2h, P < 0.05), whereas prazosin and propranolol (both 5 μg/kg i.c.v.) had no effect, suggesting that there is tonic central α 2-adrenergic inhibition of acid secretion. NPY 13–36 significantly increased acid secretion compared to control (NPY 13–36 1000pmol/kg i.c.v.: 5.6 ± 1.9mmol/2h;control: 1.3 ± 0.8mmol/2h, P < 0.05), whereas [Leu 31, Pro 34]-NPY had no effect, suggesting that the central effect of NPY is mediated at a Y 2, probably pre-synaptic receptor. Finally, i.c.v. desmethylimipramine (DMI) inhibited the acid response to i.c.v. NPY when injected before but not after NPY (i.c.v. DMI then i.c.v. NPY: control,15.2 ± 6.6mmol/2h;DMI, 3.5 ± 1.2mmol/2h, P< 0.05; i.c.v. NPY followed by i.c.v. DMI: control,8.9 ± 4.0mmol/2h;DMI, 9.9 ± 2.9mmol/2h, P > 0.05). This suggests that NPY acts by decreasing noradrenaline release. These findings are compatible with the hypothesis that i.c.v. NPY increases acid secretion by decreasing tonic central adrenergic inhibition of acid by decreasing release of noradrenaline at pre-synaptic level.