Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 433 records · Page 24Linked to original sources

PubMed1986

Pathogenesis of compound 48/80-induced gastric lesions in rats.

Intraperitoneal administration of 0.75 mg/kg of compound 48/80 (a mast cell degranulator) once daily for four days induced extensive gastric lesions in rats. Oral administration of tripelennamine (histamine H1-receptor antagonist) and cimetidine (histamine H2-receptor antagonist) twice daily for four days had little or no effect on the lesion formation. Oral administration of methysergide and cyproheptadine (serotonin antagonists) and FPL-52694 (a mast cell stabilizer) potently inhibited the compound 48/80-induced lesions. Intraperitoneal administration of histamine plus serotonin, or serotonin alone, induced gastric lesions which resembled those induced by compound 48/80. These lesions were potently inhibited by methysergide and cyproheptadine, but not by tripelennamine, cimetidine, and FPL-52694. Single or repeated administration of compound 48/80 significantly increased serum histamine and serotonin levels. After a single administration of compound 48/80, the increased histamine levels rapidly returned to normal levels, but serotonin levels remained high for 7 hr. Histamine and serotonin levels in the gastric mucosa were transiently increased after a single administration of compound 48/80, but remained normal after repeated administration. Single or repeated administration of compound 48/80 had little effect on arterial blood pressure. The compound 48/80-induced gastric lesions appear to be caused primarily by the release of serotonin, but not histamine, from extragastric sources.

Animals↗

PubMed1986

Mechanisms of protective activity of 16,16-dimethyl PGE2 and acetazolamide on gastric and duodenal lesions in rats.

16,16-Dimethyl PGE2 (16,16-dmPGE2), given orally at 10-30 micrograms/kg, had no effects on gastric acid secretion, or carbonic anhydrase activity, but did increase HCO3- secretion in both the stomach and duodenum of rats. 16,16-dmPGE2, at nonantisecretory doses, potently inhibited indomethacin- and water-immersion stress-induced gastric lesions and mepirizole-induced duodenal lesions in rats. Acetazolamide, given orally at 50 mg/kg, markedly inhibited carbonic anhydrase activity, but had no effects on gastric acid secretion and the basal and 16,16-dmPGE2-stimulated HCO3- secretion. Acetazolamide, at a nonantisecretory dose, had no effects on indomethacin-induced gastric lesions and mepirizole-induced duodenal lesions, but significantly inhibited water-immersion stress-induced gastric lesions. Combined administration of 16,16-dmPGE2 and acetazolamide did not influence the protective activity of 16,16-dmPGE2 on these lesions. The mechanism of the cytoprotective activity of 16,16-dmPGE2 may involve an increase in HCO3- secretion (nonmediated by carbonic anhydrase), while mechanisms involved in the effects of acetazolamide are apparently different.

16,16-Dimethylprostaglandin E2↗

PubMed1986

Determination of acid-neutralizing capacity in rat duodenum. Influences of 16,16-dimethyl prostaglandin E2 and nonsteroidal antiinflammatory drugs.

A model involving measurement of duodenal pH and acid-neutralizing capacity has been devised in anesthetized rats. A duodenal loop was made between the pyloric ring and the area just proximal to the outlet of the common bile duct (2 cm) and was perfused at a flow rate of 1.3 ml/min with HCl solution (1 X 10(-4) M, pH 4.0) made isotonic with NaCl. The pH of duodenal perfusate was continuously measured using a pH glass electrode of the flow type, and the amount of acid neutralized in the loop was titrated to pH 4.0 using a pH-stat method and by adding 10 mM HCl. Under normal conditions, the duodenal pH was kept around 6.0 as the result of neutralization in the loop (approximately 9 mu eq/hr). Subcutaneous administration of 16,16-dmPGE2 (10 micrograms/kg) significantly elevated the pH and increased acid-neutralizing capacity to 168.3% of normal levels. In contrast, indomethacin (5 mg/kg) and aspirin (200 mg/kg) as cyclooxygenase inhibitors or quinacrine (100 mg/kg) as a phospholipase A2 inhibitor significantly decreased both the pH and acid neutralizing capacity. After sacrifice with saturated KCl (intravenously), the pH decreased to 4.3 +/- 0.2 and the neutralizing capacity was reduced to 30% of normal values. Basal HCO3- secretion in the proximal duodenum (approximately 5 mu eq/hr), when titrated to pH 7.4, was significantly stimulated by 16,16-dmPGE2 and exposure of the mucosa for 10 min to 10 mM HCl. Neither indomethacin, aspirin, nor quinacrine had any effect on basal HCO3- secretion, but all significantly inhibited HCl-stimulated HCO3- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

16,16-Dimethylprostaglandin E2↗

PubMed1986

Induction of duodenal ulcers in rats under water-immersion stress conditions. Influence of stress on gastric acid and duodenal alkaline secretion.

We investigated the influence of stress on gastric acid and duodenal HCO3- secretion in rats, and examined whether duodenal ulcers develop in rats under stress conditions in the absence or presence of acid hypersecretion caused by histamine. Either restraint alone or restraint plus water-immersion stress induced lesions in the stomach but not in the duodenum. However, subcutaneous administration of histamine dihydrochloride (40 mg/kg every 2.5 h for a total of three times) to stressed rats produced macroscopically visible damage in the proximal duodenum as well as in the stomach within 8 h of exposure to stress, and the incidence of duodenal lesions was 100% in the water-immersion group (24.8 +/- 3.8 mm2, n = 8). Histamine alone had no effect on either region. These lesions in the duodenum caused by water immersion plus histamine were prevented by subcutaneously administered cimetidine (30, 100 mg/kg) or 16,16-dimethyl prostaglandin E2 (10, 30 micrograms/kg) in a dose-related manner, but not by atropine (1, 3 mg/kg). Restraint decreased acid secretion by 40%, and additional water immersion restored the decreased acid secretion to normal levels. Basal duodenal HCO3- secretion was decreased to about 70% of normal values (5-6 microEq/15 min) in the restraint group, and after additional water immersion further declined to the values of 1.5-2 microEq/15 min. An increase of HCO3- secretion caused by acid was significantly inhibited by water immersion but not by restraint. Histamine significantly increased acid secretion but did not affect duodenal HCO3- secretion. In the rats treated with both water immersion and histamine, acid secretion was significantly reduced by either cimetidine (100 mg/kg) or 16,16-dimethyl prostaglandin E2 (30 micrograms/kg), whereas duodenal HCO3- secretion was significantly increased by 16,16-dimethyl prostaglandin E2. Atropine had little effect on either acid or HCO3- secretion. These results suggest that exposure of rats to stress decreases duodenal HCO3- secretion and increases the susceptibility of the mucosa to acid emptied from the stomach, thereby inducing duodenal ulcers if acid hypersecretion is concomitantly present.

Animals↗

PubMed1986

A new model of duodenal ulcers induced in rats by indomethacin plus histamine.

We standardized a new method for producing duodenal ulcers in rats by administering indomethacin plus histamine, and investigated the pathogenesis. Indomethacin (5 mg/kg) was first given subcutaneously to rats fasted for 24 h, and subsequently histamine dihydrochloride (40 mg/kg) was given subcutaneously three times, at 2.5-h intervals, beginning 30 min after injection of indomethacin. This combined treatment induced one or two round lesions (9.8 +/- 1.4 mm2) in the proximal duodenum at an incidence of 100%, and a few lesions in the corpus and antrum of the stomach as well. Indomethacin or histamine alone had no effect on either the duodenum or the stomach. The lesions in the duodenum and antrum were inhibited by oral cimetidine (3-100 mg/kg) and 16,16-dimethyl prostaglandin E2 (dmPGE2) (3-30 micrograms/kg) in a dose-related manner, whereas those in the corpus were inhibited only by cimetidine. Indomethacin alone had no effect on gastric acid secretion, but did potentiate the increase of acid secretion caused by histamine. Histamine did not affect duodenal HCO3-secretion, whereas indomethacin slightly inhibited the basal HCO3-secretion and completely blocked the acid-stimulated HCO3-secretion. Intraduodenally administered cimetidine (30 mg/kg) or dmPGE2 (30 micrograms/kg) significantly inhibited acid secretion or increased HCO3-secretion, respectively, and both reduced the amount of acid emptied into the duodenum after treatment with indomethacin plus histamine. These results indicate that the development of duodenal lesions induced by indomethacin plus histamine in rats is due to both an increase in gastric acid secretion and an impairment of acid-induced duodenal HCO3-secretion. This newly established model will be useful for studying the pathogenesis of duodenal ulcers and for screening antiulcer agents.

16,16-Dimethylprostaglandin E2↗

PubMed1986

Variations of gastric transmucosal potential difference and lesion formation during hemorrhagic shock in the rat.

We measured transmucosal potential difference (PD) of the stomach in anesthetized rats before, during, and after hemorrhagic shock, and investigated the effects of various drugs on the PD and gastric lesion during this period. After hemorrhagic shock, there was a decrease of PD and an increase of luminal pH in the saline-perfused stomach, the degree of these changes being dependent on a fall in the arterial blood pressure. The graded reduction of PD in response to hemorrhagic shock was similarly observed in the acid-perfused stomach as in the saline-perfused one. However, gastric lesions developed only in the former, and a significant correlation was found between the lesion index and the fall in blood pressure, the reduction in PD, or the concentration of HCl as the perfusate. Subcutaneously administered propantheline bromide (30 mg/kg) or cimetidine (100 mg/kg) had no effect on gastric lesion and PD reduction caused by hemorrhagic shock. These lesions were significantly inhibited by 16,16-dimethyl prostaglandin E2 (10 micrograms/kg) or sulindac (100 mg/kg), a scavenger of OH., and aggravated by indomethacin (1 mg/kg), with less effect on the PD reduction. Intravenous infusion of NaHCO3 (0.5 M) also significantly prevented the lesion with a concomitant suppression of the PD reduction in response to hemorrhagic shock, but these effects were significantly reversed by pretreatment of the animals with acetazolamide (50 mg/kg). These results indicate that during hemorrhagic shock the PD may largely reflect the impairment of mucosal blood flow and may be used as an indicator of mucosal vulnerability to acid, gastric lesions develop only in the presence of exogenous acid, and production of prostaglandins and superoxide radicals may be involved in the pathogenesis of gastric lesions.

Acetazolamide↗

PubMed1986

Mechanisms of irritative activity of compound 48/80 on rat gastric mucosa.

A single intraperitoneal injection of compound 48/80 (48/80) (0.5-3 mg/kg) into anesthetized rats caused a dose-dependent reduction of the transmucosal potential difference (PD) and intraluminal pH (pH), and induced gastric lesions within 2 h. These same changes were seen with an intraperitoneal injection of histamine, but not with serotonin. There was a significant correlation between the lesion index and the PD reduction, although the integrity of the resting gastric mucosal barrier remained unaltered. The PD reduction caused by 48/80 was dose-dependently inhibited by tripelennamine (H1-antagonist) and FPL-52694 (mast cell stabilizer) and partially suppressed by methysergide (serotonin antagonist), but the changes in pH were prevented by FPL-52694 and cimetidine (H2-antagonist). The reduction of PD and pH induced by histamine was inhibited by tripelennamine or cimetidine, respectively, but these responses were not inhibited by FPL-52694 or methysergide. Gastric lesions induced by 48/80 were potently inhibited by tripelennamine and FPL-52694, and partially by cimetidine, whereas those induced by histamine were significantly prevented by tripelennamine and cimetidine, but not by FPL-52694. Methysergide had no effect on the development of gastric lesions in response to 48/80 or histamine. These results suggest that a single injection of 48/80 reduced the PD and stimulated acid secretion, thereby producing gastric lesions. These effects of 48/80 may be due to activation of H1- and H2-receptors by acutely released endogenous histamine.

Animals↗

PubMed1986

Mechanisms of antisecretory action of intragastric FPL-52694: a mast cell stabilizer in anesthetized rats.

Mechanisms of antisecretory action of intragastric FPL-52694, a mast cell stabilizer, were investigated in anesthetized rats. In Schild's rat preparation, intravenous FPL-52694 (10 mg/kg) significantly suppressed acid secretion in response to only tetragastrin (20 micrograms/kg, i.v.) (42.1 +/- 19.4%), while intragastric application of FPL-52694 (100 mg/kg) for 30 min produced a marked, unequivocal inhibition (over 70%) in acid secretory responses to histamine (1 mg/kg, i.v.) and carbachol (2.5 micrograms/kg, i.v.) as well as tetragastrin. The inhibitory effect of intragastric FPL-52694 was confirmed in the lumen-perfused rats, where acid secretion (24-25 mumol/10 min) induced by intravenous infusion of histamine (8 mg/kg/h) was abolished for 1 h after exposure of the stomach for 30 min to this agent. Inhibition of histamine-stimulated acid secretion by intragastric FPL-52694 was much greater and lasted longer (2 h) as compared with xylocaine (4% solution), but significantly mitigated by pretreatment of the rats with subcutaneous administration of indomethacin (3 mg/kg). Furthermore, application of FPL-52694 but not of xylocaine to the stomach caused a reduction of transmucosal potential difference, an increase of luminal appearance of HCO-3 (1-2 mumol/10 min), and an enhancement of H+ back-diffusion, although no damage was appreciated in the mucosa. These results suggest that antisecretory action of intragastric FPL-52694 may involve local mechanisms such as neutralization of acid with HCO-3, a loss of acid due to H+ back-diffusion, and inhibition of acid production mediated by endogenous prostaglandins, but is not related to the local anesthetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1986

[Effects of elcatonin, a synthetic analogue of eel calcitonin, on acute gastric and duodenal lesions and gastroduodenal function in rats].

We studied the effects of elcatonin (eel calcitonin), on various gastric and duodenal lesions, gastric acid and duodenal alkaline secretion, and gastric motility in rats. Elcatonin at 1-30 unit/kg, given subcutaneously, dose-dependently inhibited the development of HCl-aspirin-, HCl-ethanol-, water-immersion stress- and indomethacin-induced gastric lesions. This agent also significantly prevented the formation of duodenal lesions induced by indomethacin plus histamine at 30 unit/kg, although it showed only a tendency of inhibition against mepirizole-induced duodenal lesions. 16, 16-Dimethyl prostaglandin E2 (3-30 micrograms/kg), given orally as a reference drug, showed a potent inhibition against all types of lesions tested herein at the dose of 3 micrograms/kg or greater. Elcatonin dose-dependently inhibited gastric secretion (volume, acid and pepsin output) in pylorus-ligated rats and gastric motility in conscious rats, but had no effect on duodenal alkaline secretion in anesthetized rats. On the other hand, 16, 16-dimethyl prostaglandin E2 at 10 micrograms/kg, given intraduodenally, significantly inhibited gastric secretion and motility, but stimulated duodenal alkaline secretion. We conclude that elcatonin markedly protects the gastrointestinal mucosa from injury induced by stress or various irritants. These effects might be in part accounted for by the antisecretory and antimotility activities of this peptide, although some other unknown mechanisms may be involved in the mucosal protection afforded by elcatonin.

16,16-Dimethylprostaglandin E2↗

PubMed1986

[Effects of misoprostol, (+/-)-methyl (11 alpha, 13E)-11, 16-dihydroxy-16-methyl-9-oxoprost-13-en-l-oate, on various gastric and duodenal lesions in rats].

Male Sprague-Dawley rats (230-280 g), either fasted for 15-24 hr or non-fasted prior to experiments, were used. Misoprostol (3-100 micrograms/kg, p.o.) dose-dependently inhibited the development of 150 mM HCl X aspirin (100 mg/kg)-, 150 mM HCl X 60% ethanol-, and aspirin (150 mg/kg)-induced gastric lesions. Misoprostol (30, 100 micrograms/kg, p.o.), given twice daily for 4 days, significantly inhibited prednisolone (50 mg/kg given once daily for 4 days)-induced gastric lesions. Misoprostol (30 or 2 X 300 micrograms/kg, p.o.) also significantly inhibited water-immersion stress (21 degrees C, 10 hr)-induced gastric lesions or mepirizole (200 mg/kg)-induced duodenal lesions, respectively. In contrast, misoprostol (30-300 micrograms/kg, p.o.) had no effects on indomethacin (25 mg/kg)- and mepirizole (200 mg/kg)-induced gastric lesions. Misoprostol (30 micrograms/kg, p.o.) had no effect on gastric secretion in pylorus-ligated preparations (4 hr), but it (100 or 300 micrograms/kg, p.o.) significantly increased the volume and pepsin output. Gastric motility, either normal or enhanced with indomethacin (25 mg/kg), was inhibited by misoprostol (30 or 300 micrograms/kg, p.o.). Misoprostol (30 micrograms/kg, i.d.) significantly stimulated duodenal HCO3- secretion. Mechanisms by which misoprostol inhibits various gastric lesions remain unknown. However, the stimulatory activity on duodenal HCO3- secretion appears to be involved in the preventive effect of misoprostol on the development of duodenal lesions. The effects of cimetidine and 16,16-dimethyl PGE2 were also studied and compared with those of misoprostol.

Alprostadil↗

PubMed1986

[Effects of gastric proton pump inhibitors on gastric secretion and peptic ulcers].

This is a review article on newly developed antisecretory drugs which are now called proton pump inhibitors. Gastric H+ is secreted from the secretory membrane of parietal cells into the lumen of the stomach, using energy obtained by destructing ATP with H+, K+-ATPase (proton pump). Various substituted benzimidazoles such as timoprazole, picoprazole, omeprazole, or NC-1300 potently inhibits this proton pump at pH 6.0, thereby resulting in a strong inhibition of gastric H+ secretion. This inhibition of H+ secretion lasts for a long period, ie, 1-3 days after a single oral or intraduodenal administration, both in experimental animals and humans. This long lasting activity of these compounds appears to be due to their accumulation in the parietal cells because of their low pKa values (about 4.0). Proton pump inhibitors dose-dependently inhibit the development of various experimental ulcers and accelerate healing of chronic gastric ulcers in animals. Since these compounds also potently inhibit the development of HCl X ethanol or HCl X aspirin-induced gastric ulcers in animals, they are considered to have a cytoprotective activity. Some of the compounds (e.g., omeprazole) afforded a complete healing of peptic ulcers in man when it was given once daily for 2 to 4 weeks, without any adverse effects. Therefore, these proton pump inhibitors appear to be promising drugs for the treatment of peptic ulcer diseases.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1986

[Effects of KT1-32 on acute gastric lesions and duodenal ulcers induced in rats].

We studied the effects of KT1-32 (sodium guaiazulene 3-sulfonate) on development of various acute gastric lesions and duodenal ulcers induced in rats. Male Donryu or Sprague-Dawley rats (220-270 g), fasted (but allowed free access to water) for 24 or 48 hr before the experiments, were used. KT1-32 (dissolved in distilled water, 10-100 mg/kg), given p.o. or intraduodenally (i.d.), dose-dependently inhibited the development of gastric lesions induced by HCl X ethanol (60% ethanol in 150 mM HCl), HCl X aspirin (aspirin 100 mg/kg in 150 mM HCl) or aspirin (150 mg/kg in pylorus-ligated preparation) and Shay ulcers (14 hr pylorus ligation). KT1-32 (30 and 100 mg/kg), given p.o. twice (9.5 hr apart), significantly inhibited the development of duodenal ulcers induced by mepirizole (200 mg/kg, s.c.), but did not inhibit gastric lesions developed simultaneously. KT1-32 (30 and 100 mg/kg), given p.o. or i.d., significantly reduced gastric acid secretion when examined using pylorus ligation preparations. KT1-32 (100 mg/kg, i.d.) had no effect on basal and suppressed duodenal HCO3- secretion by mepirizole. These results suggest that KT1-32 is a promising drug for the treatment of gastritis and peptic ulcers.

Animals↗

PubMed1986

Biochemical and pharmacological analysis of 2-[(2-dimethylaminobenzyl)sulfinyl] benzimidazole (NC-1300), a new proton pump inhibitor.

Biochemical and pharmacological properties of a newly synthesized compound, 2-[(2-dimethylaminobenzyl)sulfinyl] benzimidazole (NC-1300), were studied. NC-1300, at pH 6.0, potently inhibited the activity of H+ K+ ATPase in the rabbit gastric mucosa, thereby classifying it as a proton pump inhibitor. The inhibitory efficacy of NC-1300 on the pump was much the same as that seen with omeprazole. NC-1300 had no effect on acetylcholine-stimulated ileum contraction in guinea pigs at 10(-5) M, but it non-competitively inhibited the contraction at 10(-4) M. NC-1300 had no effect on histamine-stimulated atrial beating frequency in guinea pigs at 10(-4) or 10(-5) M. NC-1300, given either intraduodenally or orally, had a potent and long-lasting (more than 24 hr) inhibitory effect on gastric secretion in pylorus-ligated rats. Pretreatment with NC-1300 dose-dependently protected the gastric mucosa from damage induced by pylorus ligation, water-immersion stress, aspirin, and indomethacin, and the duodenal mucosa from damage induced by mepirizole in rats. We conclude that the antisecretory activity of NC-1300 appears to be mainly related to an inhibition of H+ K+ ATPase, while its antigastric and antiduodenal lesion activities are primarily related to an antisecretory effect.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1986

Effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various gastric lesions induced in rats.

We studied the effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats. Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered arbaprostil dose-dependently prevented the development of HCI-ethanol-, histamine-, water-immersion stress-, or indomethacin-induced gastric erosions. Intraduodenally administered arbaprostil also dose-dependently prevented the development of aspirin-induced gastric erosions in pylorus-ligated rats. Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of acetic acid-induced gastric ulcers. However, oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of acetic acid-induced gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on ulcer healing. These results indicate that arbaprostil, at either antisecretory or even acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic gastric ulcers.

Acetates↗

PubMed1986

Vinegar is a dietary mild irritant to the rat gastric mucosa.

Exposure of the rat stomach to acetic acid (0.3-3%) caused a concentration-dependent reduction of transmucosal potential difference (PD) and increase of luminal pH (gastric alkaline response). These concentrations of acetic acid, when given topically to the stomach, significantly prevented development of gastric lesions induced by subsequent exposure to absolute ethanol, the inhibition being 42.3%, 95.8% and 70.4% at concentrations of 0.3%, 1% and 3%, respectively. Gastric alkaline response and protection of ethanol-induced gastric lesions caused by 1% acetic acid were significantly attenuated by pretreatment of the animals with indomethacin (5 mg/kg, s.c.). Although other related carboxylic acids at 1% concentration such as citric acid (52 mM), maleic acid (86 mM) and formic acid (217 mM) affected both PD and luminal pH in varying degrees, these agents, except for 1% maleic acid, failed to prevent gastric lesions in response to absolute ethanol. Similar to 1% acetic acid (167 mM), gastric alkaline response and adaptive cytoprotection induced by 1% maleic acid were significantly antagonized by pretreatment with indomethacin. Formic acid also induced a significant gastric alkaline response, but this effect was not effected by indomethacin. These results suggest that dilute acetic acid such as vinegar (approximately 3% acetic acid) acts as a mild irritant to the stomach, and induces alkaline response and adaptive cytoprotection, mediated by endogenous prostaglandins. Other related carboxylic acids may have similar effects, but those depend upon the concentrations used.

16,16-Dimethylprostaglandin E2↗

PubMed1986

Augmentation of cysteamine and mepirizole-induced lesions in the rat duodenum and stomach by histamine or indomethacin.

Repeated administration of histamine X 2HCl (40 mg/kg X 4) significantly augmented mepirizole (200 mg/kg) or cysteamine (300 mg/kg)-induced duodenal and gastric lesions in rats within 6 hr. Most of the duodenal lesions were penetrating ulcers and were located over the entire duodenum. Gastric lesions were mainly located in the antrum adjacent to the duodenum. Indomethacin pretreatment did not significantly augment the duodenal lesions induced by mepirizole or cysteamine, but did augment the gastric lesions induced by these compounds.

Animals↗

PubMed1986

Gastroduodenal HCO3-secretion in anesthetized rats: effects of 16,16-dimethyl PGE2, topical acid and acetazolamide.

Alkaline secretion was measured in the whole stomach and in the proximal duodenum (2 cm proximal to the outlet of the common bile duct) of anesthetized rats, under basal conditions and in response to topical acid and 16,16-dimethyl PGE2 (16-dmPGE2) given by various routes. Gastric alkaline secretion was unmasked by intraduodenal administration of omeprazole (30 mg/kg). Both the stomach and duodenum consistently secreted bicarbonate in amounts of 0.2-0.4 microEq/15 min and 1.5-2 microEq/15 min as a basal secretion, respectively. 16-dmPGE2, either given subcutaneously (1-30 micrograms/kg), intravenously (3 micrograms/kg/hr) or by topical application for 30 min (0.3-10 micrograms/ml), (concentration)-dependently increased HCO3- secretion in both tissues, but this effect disappeared quickly after sacrifice with KCI (i.v.). Stimulation of HCO3- secretion was also caused by topical acid to the stomach (100 mM HCI for 10 min) or to the duodenum (10 mM HCI for 10 min), but was completely blocked by pretreatment with indomethacin (5 mg/kg, s.c.). Acetazolamide, given subcutaneously at 100 mg/kg, which gives over 80% inhibition of carbonic anhydrase activity in the gastroduodenal mucosa, had no effect on either basal or stimulated HCO3- secretion caused by 16-dmPGE2 (10 micrograms/kg, s.c.). These results indicate that both endogenous and exogenous (16-dmPGE2) prostaglandins stimulate alkaline secretion in the gastroduodenal mucosa of rats, and this mechanism is independent from the carbonic anhydrase activity of the tissue.

16,16-Dimethylprostaglandin E2↗

PubMed1986

Cytoprotective effects of NC-1300 and omeprazole on Hcl . ethanol-induced gastric lesions in rats.

NC-1300 (10-100 mg/kg), given p.o. at 0.5, 6, 12 or 24 hr before HCl . ethanol, dose-dependently protected the rat gastric mucosa. This protection was observed even when the gastric contents had been removed before application of HCl . ethanol. NC-1300 (30 mg/kg), given i.p., was without effect on lesion formation in a dose which potently inhibited gastric acid secretion in pylorus-ligated rats. pretreatment with indomethacin (5 mg/kg, s.c.) resulted in no reduction in the protection by NC-1300, excluding the possible participation of endogenous prostaglandins in the protective mechanism. N-ethylmaleimide pretreatment (10 mg/kg, s.c.) slightly reduced the protective activity of NC-1300, suggesting the partial participation of endogenous sulfhydryl compounds in the NC-1300 protection. NC-1300 sulfide and mercaptobenzimidazole (compounds obtained after mixing NC-1300 with acidic solution) also dose-dependently protected against HCl . ethanol-induced lesions when given p.o. at 0.5 hr before HCl . ethanol. The protection was significant but was considerably reduced in contrast to NC-1300 when the compounds were given 12 hr beforehand. NC-1300 sulfone had no effect on lesion formation. Omeprazole (10, 30 mg/kg), given p.o., also dose-dependently inhibited HCl . ethanol-induced lesions. However, the duration of protection was shorter than that seen with NC-1300, i.e., the effect disappeared 12 hr later. Thus, NC-1300 has a potent and long-lasting activity on HCl . ethanol-induced gastric lesions. The mechanism by which this occurs remains unknown.

2-Pyridinylmethylsulfinylbenzimidazoles↗