Gastric Acid Secretion In Rats Research Articles

Stimulation of Gastric Acid Secretion by Centrally Administered Orexin-A in Conscious Rats

Orexins are novel neuropeptides that are localized in neurons within the lateral hypothalamus and regulate feeding behavior. The lateral hypothalamus also plays an important role in the central regulation of gut function. We therefore hypothesized that orexins might be involved in the central control of gastric acid secretion. To address this question, we examined the effect of central injection of orexins on gastric acid secretion in rats. Intracisternal injection of synthetic orexin-A but not orexin-B dose-dependently stimulated acid secretion while intraperitoneal administration of orexin-A failed to stimulate acid secretion. Vagotomy or atropine abolished the action by central orexin-A. These data suggest for the first time that orexin-A may act in the brain to stimulate gastric acid secretion by modulating the vagal system. Considering its stimulatory action on feeding, we hypothesize here that orexin-A is a candidate mediator of cephalic phase gastric secretion.

Pretreatment with SR48692 has different effects on central neurotensin-induced gastric mucosal defense and inhibition of gastric acid secretion in rats

Neurotensin is a tridecapeptide present in the brain and gastrointestinal tract. Administration of neurotensin into the brain results in responses in the gastrointestinal tract, suggesting a role for neurotensin in the interrelationships that comprise the brain–gut axis. Intracerebroventricular (i.c.v.) administration of neurotensin protects the gastric mucosa against injury caused by cold water restraint (CWR) and also inhibits gastrin-stimulated gastric acid secretion. The hypothesis tested was that these two actions of neurotensin are mediated via its high-affinity receptor. Rats were given neurotensin (60 μg, i.c.v.) prior to CWR or pylorus ligation after pretreatment with SR48692, a nonpeptide antagonist of the high-affinity neurotensin receptor (0.25 or 2.5 μg, i.c.v., or 10, 100, or 500 μg kg −1, i.p.). Neurotensin reduced cold water restraint (CWR)-induced gastric mucosal injury and inhibited gastrin-stimulated acid secretion. Pretreatment with SR48692 (2.5 μg, i.c.v., or 100 μg kg −1, i.p.) prior to CWR blocked neurotensin's protection of the gastric mucosa against injury. In contrast, pretreatment with 2.5 μg SR48692, i.c.v., did not block neurotensin-induced inhibition of acid secretion, whereas 500 μg kg −1, i.p., partially blocked the inhibition. SR48692 (2.5 μg, i.c.v.) inhibited acid secretion, suggesting that SR48692 has agonist activity in this system. These results suggest that central neurotensin protects the gastric mucosa against CWR-induced injury via its high-affinity receptor. The receptor that mediates central neurotensin-induced inhibition of gastric acid secretion does not appear to be the high-affinity receptor since the neurotensin receptor antagonist SR48692, when given i.c.v., had agonist activity, inhibiting stimulated acid secretion. High-affinity neurotensin receptors in the periphery appear to play a role in inhibition of stimulated gastric acid secretion.

PYY-preferring receptor in the dorsal vagal complex and its involvement in PYY stimulation of gastric acid secretion in rats.

1. Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the pharmacological profile of the receptor mediating the acid secretory response to PYY. 2. [Pro34]rat(r)/porcine(p)PYY and [Pro34]human(h)PYY (23-117 pmol), microinjected unilaterally into the DVC resulted in a similar maximal increase in net acid secretion reaching 68+/-11 and 89+/-31 micromol 90 min(-1) respectively. 3. Rat/hNPY and pNPY (47 pmol) microinjected into the DVC induced a similar net gastric acid secretion (27+/-8 and 23+/-8 micromol 90 min(-1) respectively) and a higher dose (116 pmol) tended to reduce the response. 4. Pancreatic polypeptide (PP, 4-46 pmol), [Leu31,Pro34]r/hNPY (47 and 117 pmol) and the Y2 selective agonists, hPYY3-36, pNPY5-36 and PNPY13-36 (25-168 pmol) microinjected into the DVC failed to influence basal gastric acid secretion. 5. The rank order of potency of PYY > or = [Pro34]r/pPYY = [Pro34]hPYY> r/hNPY = pNPY to stimulate gastric acid secretion upon injection into the DVC and the ineffectiveness of PP, [Leu31,Pro34]NPY and C-terminal NPY/PYY fragments suggest that a PYY-preferring receptor subtype may be involved in mediating the stimulating effect.

Interaction between gastrin and non-gastrin acid stimulating peptide in human islet cell tumors on gastric acid secretion in rats

Interaction between gastrin and non-gastrin acid stimulating peptide in human islet cell tumors on gastric acid secretion in rats

Role of nitric oxide in regulation of gastric acid secretion in rats: effects of NO donors and NO synthase inhibitor.

1. The role of nitric oxide (NO) in the regulation of acid secretion was examined in the anaesthetized rat. 2. A rat stomach was mounted in an ex vivo chamber, instilled with 2 ml of saline every 15 min, and the recovered sample was titrated at pH 7.0 against 0.1 N NaOH by use of an automatic titrator for acid secretion. Gastric mucosal blood flow (GMBF) was measured simultaneously by laser Doppler flowmeter. 3. Intragastric application of NO donors such as FK409 (3 and 6 mg ml[-1]) and sodium nitroprusside (SNP; 6 and 12 mg ml[-1]) as well as i.p. administration of cimetidine (60 mg kg[-1]), a histamine H2-receptor antagonist, significantly inhibited the increase in acid secretion in response to pentagastrin (60 microg kg(-1) h(-1), i.v.), in doses that increased gastric mucosal blood flow (GMBF). 4. Intragastric application of FK409 (6 mg ml[-1]) increased both basal and stimulated acid secretion induced by YM-14673 (0.3 mg kg(-1), i.v.), an analogue of thyrotropin-releasing hormone (TRH), but had no effect on the acid secretory response induced by histamine (4 mg kg(-1) h(-1), i.v.). 5. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1), i.v.) did not affect basal acid secretion, but significantly potentiated the increase in acid secretion induced by YM-14673 and slightly augmented the acid secretory response to pentagastrin. 6. Both pentagastrin and YM-14673 increased the release of nitrite plus nitrate (NOx), stable NO metabolites, into the gastric lumen, and these changes were completely inhibited by prior administration of L-NAME (10 mg kg(-1), i.v.). 7. Pentagastrin caused an increase in luminal release of histamine and this response was significantly suppressed by intragastric application of FK409 (6 mg ml[-1]). 8. These results suggest that either exogenous or endogenous NO has an inhibitory action on gastric acid secretion through suppression of histamine release from enterochromaffin-like (ECL) cells.

Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats.

Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.

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.

Caloric restriction causes secretagogue specific changes of gastric acid secretion in rats

The purpose of this study was to examine the effects of short-term caloric restriction (CR) for 4, 8 and 16 weeks on gastric acid secretion in rats. CR rats were fed 60% of normal food intake for 4, 8 or 16 weeks and then prepared with gastric fistulas. Histamine- and carbachol-stimulated gastric acid secretion were significantly ( P<0.05) decreased after more than 4 weeks and 8 weeks of caloric restriction, respectively. In contrast, gastrin-stimulated acid secretion was unaffected by CR. The 1-h-integrated acid output to a submaximal dose of gastrin (40 μg·kg −1) was significantly higher than that of histamine (5 mg·kg −1) after 8 weeks of CR (63±13 and 27±4 μEq·h −1, respectively). Gastrin treatment (5 μg·kg −1·h −1) of CR rats restored the gastric acid responses to both histamine and carbachol. These results suggest that CR can selectively decrease the gastric acid responses to both histamine and carbachol by depletion of the endogenous tissue stores of gastrin. More importantly, these results indicate that under an in vivo gastrin-diminished condition, histamine is not the final secretagogue for gastric acid secretion.

Effect of quinacrine, a phospholipase A2 inhibitor on stress and chemically induced gastroduodenal ulcers.

Quinacrine, a phospholipase A2 inhibitor, has been studied for its ability to inhibit gastric secretion and to protect the gastric and duodenal mucosa against chemically and stress-induced ulcers. Acid secretion studies were undertaken in pylorus-ligated rats with and without quinacrine treatment. Experimental gastric lesions were induced by water-immersion restraint stress, indomethacin and 80% ethanol in rats; whereas duodenal ulcers were produced by treatment of rats with cysteamine. The level of nonprotein sulfhydryl compounds and gastric wall mucus were also measured in the glandular stomach of the rats following ethanol-induced gastric lesions. The results of this study demonstrate that quinacrine produces a dose-dependent inhibition of gastric acid secretion in rats. Pretreatment with quinacrine significantly attenuated the formation of stress-, indomethacin- and ethanol-induced gastric lesions. Quinacrine also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of quinacrine was associated with appreciable inhibition of ethanol-induced depletion of nonprotein sulfhydryls and gastric wall mucus. These findings point towards the mediation of sulfhydryls in quinacrine-induced gastrointestinal cytoprotection. In conclusion, this study demonstrates that quinacrine possesses significant antiulcer and cytoprotective activity against various experimentally induced gastroduodenal lesions. Although the mechanism of action of quinacrine requires further evaluation, the experimental observations derived from this study may have future clinical relevance and therefore deserve to be investigated thoroughly.

Role of gastrin/CCK-B receptor in the regulation of gastric acid secretion in rat.

The aim of this study was to investigate whether gastrin regulates morphological changes and alpha-subunit gene expression in parietal cells through the gastrin/CCK-B receptor on enterochromaffin-like cells by histamine release. Treatment with 100 mg/kg of YM022, a potent and selective gastrin/CCK-B receptor antagonist, for one week in rats did not alter mRNA levels of histidine decarboxylase or H+, K+-ATPase. However, parietal cell morphology predominantly changed to the resting form, although the serum gastrin concentration was significantly increased. Additional treatment with YM022 and oral omeprazole, 100 mg/kg, for one week markedly suppressed the increases of mRNA levels of histidine decarboxylase and H+, K+-ATPase and completely blocked the morphological transformation of the parietal cells to a stimulated form induced by treatment with omeprazole alone. This indicates that the morphological transformation of parietal cells to an activated form with a subsequent increase in H+, K+-ATPase synthesis caused by hypergastrinemia is mediated by increased histidine decarboxylase gene expression in enterochromaffin-like cells via gastrin/CCK-B receptors.

Centrally applied nitric oxide donors inhibit vagally evoked rat gastric acid secretion: involvement of sympathetic outflow.

ntracerebroventricularly (i.c.v.) administered nitric oxide (NO) donors, 3-morpholinosydnonimine (SIN-1) (100-500 microg/animal) and sodium nitroprusside (SNP) (100-250 microg/animal) dose-dependently inhibited the rat gastric acid secretion evoked by vagal stimulation at 3 Hz. Furthermore, the inhibitory effect of SIN-1 (250 microg/animal) was more marked and its onset was more rapid than that of SNP (250 microg/animal). The SIN-1 (250 microg/animal)-induced antisecretory effect was abolished by both splanchnicotomy and phentolamine (5 mg/kg, i.m.), and also by indomethacin (500 microg/animal, i.c.v.). These results suggest that i.c.v. administered NO donors inhibit vagally evoked gastric acid secretion by activation of central sympathetic outflow. Central prostaglandin is probably implicated in this NO-mediated antisecretory effect.

Centrally Applied Nitric Oxide Donors Inhibit Vagally Evoked Rat Gastric Acid Secretion: Involvement of Sympathetic Outflow

Centrally Applied Nitric Oxide Donors Inhibit Vagally Evoked Rat Gastric Acid Secretion: Involvement of Sympathetic Outflow

Identification and biological activity of novel peptidomimetic gastrin/CCK-B receptor agonists

The design, synthesis and biological activity of two novel series of compounds derived from the basic Boc-CCK-4 structure which provide potent ligands for the gastrin/CCK-B receptor is outlined. Within these series, new pseudopeptide compounds were discovered which unexpectedly were functional agonists in vivo, as shown by their ability to stimulate basal gastric acid secretion in rats, an effect which was blocked by the potent gastrin/CCK-B receptor antagonist YM022.

EFFECTS OF CARNITINE AND ITS DERIVATIVES ON GASTRIC ACID SECRETION IN RATS

Carnitine is a natural substance that acts as a carrier of fatty-acids across the inner mitochondrial membrane for subsequent β-oxidation. Acetyl- L-carnitine is the acetyl derivative of L-carnitine that has been shown to possess a slight cholinomimetic activity. Its success in sports medicine is dependent on the fact that it is able to stimulate the central nervous system functions. This study aims to investigate the effects of L-carnitine (LC) and its derivatives—acetyl- L-carnitine (ALC) and propionyl- L-carnitine (PLC)—on gastric acid secretion in rats. A concentration-dependent relationship with both ALC or PLC was observed in experiments in vitrousing a rat isolated stomach. The addition of atropine to the perfusion bath only partially antagonized the effects of the two compounds. Stimulation of gastric acid secretion in a dose-dependent manner was also found when the tested compounds were administered i.v. to anaesthetized rats. To elucidate the mechanism of the gastric secretory response, assay for acetylcholine esterase activity using acetylthiocholine as substrate, was performed. It was found that ALC and PLC inhibited acetylcholine esterase, however, the IC 50for both compounds was about four times of magnitude greater than that of eserine. As the increase of the gastric acid secretion promoted by carnitines was blocked only partially by atropine both in vitroand in vivo, whilst it was completely abolished by experimental degeneration of the sympathetic neurons or by blockade of the postsynaptic sympathetic receptors, it is suggested that the effect of carnitines is determined by cholinergic and partly by adrenergic mechanisms.

Comparison of the Effects of Over-the-counter Famotidine and Calcium Carbonate Antacid on Postprandial Gastric Acid

To compare an over-the-counter histamine2-receptor antagonist with an antacid as gastric acid reducers. Randomized, double-blind, placebo-controlled crossover trial. Gastric secretory research laboratory in a Veterans Affairs medical center. Eighteen healthy volunteers (10 men and 8 women) aged 25 to 62 years with normal gastric acid secretion rates. The subjects received the histamine2-receptor antagonist famotidine (Pepcid AC, 10 mg), calcium carbonate antacid tablets (Tums, 1000 mg), or placebo medications 1 hour after a test meal. Two identical meals were taken 2.5 and 6.0 hours after the medication was given. Intragastric pH was maintained at 4.0 by in vivo intragastric titration with 0.3N sodium bicarbonate for 10 hours (1 hour before and 9 hours after medication). Reduction in sodium bicarbonate titrant use in the 2 treatment groups compared with titrant use with placebo was reflective of acid secretion inhibited by a famotidine or acid neutralized by calcium carbonate tablets. When evaluated in increments of 30 minutes, calcium carbonate had a rapid onset of action, neutralizing 6.7 mmol of acid in the first 30 minutes. However, its duration of effect was only 60 minutes. Famotidine had a delayed onset of action compared with antacid, beginning after 90 minutes. However, famotidine had a duration of effect of at least 540 minutes. At its peak effect, 210 minutes after administration, famotidine reduced acid secretion by 7.3 mmol per 30 minutes. Recommended over-the-counter doses of famotidine and calcium carbonate tablets have different pharmacokinetic profiles when taken in the postprandial period. The antacid has a rapid onset and short duration of action, while the histamine2-receptor antagonist has a delayed onset and a prolonged duration. Their peak potencies are similar.

Reversal by NPY, PYY and 3-36 molecular forms of NPY and PYY of intracisternal CRF-induced inhibition of gastric acid secretion in rats.

1. The Y receptor subtype involved in the antagonism by neuropeptide Y (NPY) of intracisternal corticotropin-releasing factor (CRF)-induced inhibition of gastric acid secretion was studied in urethane-anaesthetized rats by use of peptides with various selectivity for Y1, Y2 and Y3 subtypes: NPY, a Y1, Y2 and Y3 agonist, peptide YY (PYY), a Y1 and Y2 agonist, [Leu31, Pro34]-NPY, a Y1 and Y3 agonist, NPY(3-36) and PYY(3-36), highly selective Y2 agonists and NPY(13-36) a weak Y2 and Y3 agonist. Peptides were injected intracisternally 10 min before intracisternal injection of CRF (10 micrograms) and gastric acid secretion was measured by the flushed technique for 1 h before and 2 h after pentagastrin-(10 micrograms kg-1 h-1, i.v.) infusion which started 10 min after CRF injection. 2. Intracisternal injection of CRF (10 micrograms) inhibited by 56% gastric acid secretion stimulated by pentagastrin. Intracisternal injection of NPY and PYY (0.1-0.5 microgram) did not influence the acid response to pentagastrin but blocked CRF-induced inhibition of pentagastrin-stimulated acid secretion. NPY(3-36) (0.5 microgram) and PYY(3-36) (0.25 and 0.5 microgram) also completely blocked the inhibitory action of CRF on pentagastrin-stimulated acid secretion. 3. [Leu31, Pro34]-NPY (0.5-5 micrograms) and NPY(13-36) (0.5-5 micrograms) injected intracisternally did not modify gastric acid secretion induced by pentagastrin or CRF inhibitory action. 4. The sigma antagonist, BMY 14802 (1 mg kg-1, s.c.) did not influence the acid response to pentagastrin but prevented the antagonism by PYY(3-36) (0.5 microgram) of the CRF antisecretory effect. 5. These results show that both PYY and NPY and the 3-36 forms of PYY and NPY are equipotent in blocking central CRF-induced inhibition of pentagastrin-stimulated gastric acid secretion. The structure-activity profile suggests a mediation through Y2 receptor subtype and the involvement of sigma binding sites.

Gastric Enterochromaffin-Like Cells and the Regulation of Acid Secretion

The interaction of gastrin, somatostatin, and other transmitters at the level of the histamine-containing enterochromaffin (ECL) cell is the major pathway determining rate of gastric acid secretion. Gastrin stimulates ECL cell elevation of [Ca2+]i, synthesis of histidine decarboxylase, histamine release, and cell growth by binding at a cholecystokinin-B receptor. Somatostatin inhibits gastrin-dependent elevation of [Ca2+]i and hence histamine release by binding to stomatostatin receptor 2 subtype.

Inhibition of vagally mediated gastric acid secretion by activation of central prostanoid EP3 receptors in urethane-anaesthetized rats.

1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostanoid EP receptor ligands on vagally stimulated gastric acid secretion in rats anaesthetized with urethane. 2. Administration of misoprostol (EP3/EP2 receptor agonist) and sulprostone (EP3/EP1 receptor agonist) reduced vagally mediated gastric acid secretion in a dose-dependent manner (0.1, 0.3 and 1.0 nmol per animal). Butaprost (EP2 receptor agonist) (0.3 and 3.0 nmol per animal) was without effect. 17-Phenyl-omega- trinor PGE2 (EP1/EP3 receptor agonist) attenuated vagally mediated gastric acid secretion only at its highest dose (1.0 nmol per animal); this antisecretory effect was not prevented by pretreatment with SC-19220 (selective EP1 receptor antagonist) (20 nmol per animal, i.c.v.). 3. The potency of these test agents in attenuation of vagally mediated gastric acid secretion was as follows: misoprostol > or = sulprostone > > 17-phenyl-omega-trinor PGE2 > > > butaprost. These results suggest that activation of central prostanoid EP3 receptors induces inhibition of vagally mediated gastric acid secretion in rats.

Synthesis and biological activity of 1-alkylcarbonylmethyl analogues of YM022

A novel series of 1-alkylcarbonylmethyl analogues of the potent gastrin/CCK-B receptor antagonist YM022 have been prepared. A number of analogues retained good affinity for the gastrin/CCK-B receptor and one compound ( 6d) showed improved binding and enhanced selectivity for this receptor over CCK-A. A second compound ( 6j) gave improved in vivo inhibition of gastric acid secretion in rats. Both analogues were shown to have significantly better activity in the same model following i.d. dosing than either YM022 or L-365,260.

Effects of Cuban analog (SWR-104SA), a new histamine H2 receptor antagonist, on gastric acid secretion and experimental ulcer formation

The antagonism of histamine H2-receptor by SWR-104SA (1'-bromo-N-[3-[3-(1-piperidinylmethyl) phenoxy] propyl]-spiro [1,3-dioxolane-2,9'-pentacyclo-[4.3.0.0.(2,5)0.(3,8) 0.(4,7)]nonane]-4'-carboxamide monooxalate) was estimated using the isolated guinea-pig atrium and gastric acid secretion in rats. The concentration-response curves for the positive chronotropic effect of histamine on the atrium were displaced to the right in parallel without change in the maximum response by SWR-104SA and roxatidine acetate hydrochloride (roxatidine). The pA2 values of SWA-104SA and roxatidine acetate hydrochloride were 7.27 and 7.38, respectively. The slopes of the regression line of log (DR-1) against log SWR-104SA and roxatidine concentration were 1.00 and 0.92, respectively. There was no significant difference between the two compounds with respect to the histamine H2-receptor antagonism and/or binding manner in vitro. In the rat gastric fistula model stimulated by histamine, however, antisecretory potency of SWR-104SA was 3 times less than that of roxatidine. SWR-104SA given p.o. prevented the formation of gastric lesion induced by HCl-ethanol and indomethacin dose-dependently, roxatidine also prevented its formation by HCl-ethanol, but failed to prevent that by indomethacine. These antiulcer activities of SWR-104SA were shown at the lesser doses of antisecretory activity. On the other hand, roxatidine did not prevent the ulcer formation at the same dose level of antisecretory activity. These results indicate that the antiulcer effect of SWR-104SA is not caused by the antisecretory action alone. In addition, the mucosal protective activity of SWR-104SA for HCl-ethanol induced gastric lesion was independent of endogenous prostaglandins. Moreover SWR-104SA had inhibitory effects on indomethacin-induced gastric hypermotility in rats. These actions may partly explain the gastric protection of this compound and additional mechanisms such as mucosal blood flow could be involved in the antiulcer efficacy. Consequently, it appears that SWR-104SA is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.