Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 397 records · Page 22Linked to original sources

PubMed1989

Stimulation of gastric alkaline secretion by histamine in rats: possible involvement of histamine H2-receptors and endogenous prostaglandins.

The mechanism of stimulatory action of histamine on gastric alkaline secretion was investigated in anesthetized rats. Intravenous infusion of histamine (2-8 mg/kg/hr) dose-dependently stimulated acid secretion and in the presence of omeprazole (60 mg/kg), an H+/K+-adenosine triphosphatase inhibitor, produced an increase of gastric but not duodenal alkaline secretion; the degree of gastric alkalinization was also dependent on the dose of histamine, reaching the maximal values of approximately 1.0 microEq/10 min. Cimetidine (100 mg/kg s.c.) significantly inhibited both acid and alkaline secretory responses caused by histamine, whereas indomethacin (5 mg/kg s.c.) significantly prevented the increased alkaline secretion caused by histamine as well as mucosal acidification (100 mM HCl for 10 min). Tripelennamine (10 mg/kg s.c.) had no effect on either acid or alkaline secretion. Histamine (8 mg/kg/hr) reduced the arterial blood pressure (25.3%) and increased the mucosal vascular permeability in the stomach as determined by Evans blue (160%), but these vascular responses were significantly prevented only by tripelennamine, excluding the possible contribution of the vascular effects to the increased gastric alkaline secretion. These results suggest that histamine may stimulate gastric alkaline secretion as well as acid secretion, and the mechanism of histamine-induced alkaline secretion may involve both endogenous prostaglandins and stimulation of H2-receptors.

Animals↗

PubMed1989

Role of sulfhydryls in mucosal injury caused by ethanol: relation to microvascular permeability, gastric motility and cytoprotection.

The relationship between gastric mucosal glutathione (GSH) levels, vascular permeability, gastric motility and mucosal injury caused by ethanol was investigated in rats. Oral administration of 50% ethanol (1 ml) produced elongated reddish bands of lesions in the mucosa with a significant reduction of GSH levels and increase of microvascular permeability. These lesions were significantly inhibited by pretreatment with s.c. administered diethylmaleate (DEM: 1 ml/kg), cysteamine (100 mg/kg) and 16, 16-dimethyl prostaglandin E2 (dmPGE2, 10 micrograms/kg) but worsened markedly by N-ethylmaleimide (NEM: 10 mg/kg). Irrespective of whether the animals were treated with 50% ethanol or not, the mucosal GSH levels were significantly decreased or increased, respectively, by DEM or cysteamine, and were not affected by both NEM and dmPGE2. NEM significantly enhanced the vascular permeability in the absence or presence of ethanol (greater than 10%), whereas other agents significantly inhibited only the increased vascular permeability caused by ethanol. On the other hand, gastric motility was potently and persistently inhibited by either DEM, cysteamine or dmPGE2 at the doses which prevented ethanol-induced mucosal injury, whereas NEM had no effect on the motility. These results suggest that 1) the mucosal GSH levels do not relate directly to either development or prevention of ethanol-induced gastric injury, 2) potentiation by NEM of the mucosal injury may be accounted for by its enhancement of the vascular permeability and 3) inhibition of gastric motility may be associated with prevention of mucosal lesions.

16,16-Dimethylprostaglandin E2↗

PubMed1988

Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats.

Effects of atropine, cimetidine, and 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) on indomethacin-induced gastric lesions were investigated in rats by correlating their effects on gastric acid and HCO3- secretion and motility. Subcutaneously administered indomethacin (25 mg/kg) produced gastric mucosal lesions within 4 hr. In parallel studies, an equivalent dose of indomethacin inhibited gastric HCO3- secretion, and stimulated gastric motor activity measured as intraluminal pressure recordings, whereas acid secretion was unaffected. The lesions induced by indomethacin were significantly prevented by three agents: cimetidine (100 mg/kg), which reduced acid secretion; atropine (1 mg/kg), which reduced acid secretion and gastric motility; and 16,16-dmPGE2 (10 micrograms/kg), which reduced acid secretion and motility and increased gastric HCO3- secretion. If acid (150 mM HCl) was infused into the stomach (1.2 ml/hr) during indomethacin treatment, only the latter two agents significantly prevented the formation of gastric lesions in response to indomethacin. Since only the effect on gastric motility was common to these two agents (atropine and 16,16-dmPGE2), the increased gastric motility may be an important pathogenetic factor in indomethacin-induced gastric lesions. The presence of acid as well as a deficiency of endogenous PGs may be prerequisite for later extension of the lesions but cannot account for the induction of mucosal lesions in rats following administration of indomethacin.

16,16-Dimethylprostaglandin E2↗

PubMed1988

Effects of dopamine on gastric mucosal lesions induced by ethanol in rats. Possible involvement of antigastric motor activity mediated with alpha 2-adrenoceptors.

Acidified ethanol (60% ethanol in 150 mM HCl, per os) induced elongated bands of hemorrhagic lesions along the long axis of the stomach within 1 hr in rats. Pretreatment with dopamine hydrochloride (DA: 1-10 mg/kg, subcutaneously) dose-dependently reduced the severity of these lesions. In parallel study, DA had no effect on acid secretion but inhibited gastric motor activity in a dose-related manner. The inhibitory effects of DA on both acidified ethanol-induced lesions and gastric motor activity were significantly reversed by pretreatment with yohimbine, an inhibitor of alpha 2-adrenoceptors (5 mg/kg, subcutaneously), but not by prazosin, haloperidol, or indomethacin. Similar to DA, both norepinephrine (NE: 1 mg/kg, subcutaneously) and epinephrine (EPI: 1 mg/kg, subcutaneously) showed inhibition of the motor activity and gastroprotection against acidified ethanol, but these effects were also significantly attenuated by yohimbine. A highly significant relationship was found between the inhibitory effects of DA, NE, and EPI on the motor activity and the mucosal lesions (r = 0.8577, P less than 0.05). In addition, administration of gentian violet (0.5% w/v, per os) stained the mucosa deep blue as elongated wide bands in the corpus region, and such localized staining was significantly prevented by DA, suggesting a flattening of the mucosal foldings in the presence of DA. These results suggest that DA (and other catecholamines) protects the rat gastric mucosa against injury caused by acidified ethanol, probably through inhibition of gastric motor activity mediated with stimulation of alpha 2-adrenoceptors.

Animals↗

PubMed1988

Effects of gastric distension and prostaglandin on acid ethanol-induced mucosal lesions in the rat.

The effects of gastric distension on the morphology of acidified ethanol (AE) -induced mucosal lesions and on the protective action of 16,16-dm PGE2 were investigated in rats. AE (50% ethanol in 150 mM HCl) was given by gavage in the intact stomach or through a fistula prepared in the forestomach in the pylorus-ligated stomach. AE produced elongated bands of hemorrhagic necrosis within 1 hr in the former, while in the pylorus-ligated stomach the shape of lesions varied depending upon the volume of irritant. One milliliter produced bandlike lesions, whereas 2 ml or more induced widespread lesions; such volumes were observed to remove the mucosal folds. 16,16-dm PGE2 (0.3-10 micrograms/kg, subcutaneous) dose dependently reduced bandlike lesions in the intact stomach, but had no or little effect on non-band-like lesions in the pylorus-ligated stomach. This agent (10 micrograms/kg) had a slight effect on the reduction of PD caused by 10-min exposure of the stomach to AE (2 ml) in the intact stomach, while such effects were not apparent in the pylorus-ligated stomach. Oral gentian violet (2 ml, 0.3% w/v) produced bandlike staining of the mucosa in intact rats, but the effect was blocked by pyloric ligation. 16,16-dm PGE2 also significantly prevented the localized staining pattern seen in intact rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Importance of pepsin and stomach distension in morphological alterations of stress-induced gastric lesions in pylorus-ligated rats.

Pylorus ligation changed the morphology and location of gastric lesions induced by water-immersion stress (WI stress) in rats; linear lesions in the corpus mucosa disappeared, and punctate lesions appeared in both the corpus and antrum, in association with the loss of H+ and the gain of Na+ in the gastric contents. Oral administration of antipeptic drugs such as amylopectin sulfate and sulfated glyptide or porcine pepsin significantly prevented or aggravated the lesions, respectively, although another type of elongated lesion appeared in response to high doses of antipeptic drugs. These antipeptic drugs or exogenous pepsin significantly reduced or increased pepsin activity, respectively, without effect on the acid output. Similar punctate lesions were produced in the atropinized rats (10 mg/kg) by instillation of acid solution (100 mM HCl plus 54 mM NaCl) with pepsin into the pylorus-ligated stomach and subjecting to WI stress. On the other hand, when the gastric contents were drained through a fistula to prevent accumulation of gastric juice in the pylorus-ligated stomach, WI stress again induced linear lesions only in the corpus mucosa. Acid hypersecretion in these rats induced by intravenous infusion of histamine, tetragastrin, or carbachol significantly aggravated the severity of lesions but did not change their morphology. These results suggest that pepsin in the presence of acid is prerequisite for development of gastric lesions in pylorus-ligated rats induced by WI stress. The morphological alterations may be accounted for by the distensions of the stomach due to accumulation of gastric juice in the lumen caused by pylorus ligation, but not due to acid hypersecretion.

Animals↗

PubMed1988

Effects of hemorrhagic shock on alkaline secretion and mucosal tolerance to acid in rat duodenum. A comparative study with indomethacin.

The effects of hemorrhagic shock (HE) on duodenal HCO3- secretion and mucosal tolerance to acid were investigated in anesthetized rats and compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 50 mm Hg (3 ml bleeding per 200 g of body weight) with a significant decrease in arterial pH and [HCO3-], and indomethacin was given subcutaneously in a dose of 5 mg/kg. The proximal duodenum (1.7 cm) secreted HCO3- at the rate of 1.5-1.8 mueq/15 min (3.5-4.2 mueq/cm/hr), and responded to luminal acid (10 mM HCl for 10 min) by a significant rise in HCO3- output. Indomethacin had no effect on basal HCO3- output but significantly inhibited the acid-induced HCO3- secretion, while under HE conditions duodenal HCO3- output significantly declined and failed to increase in response to luminal acidification. Subcutaneously administered 16,16-dmPGE2 (30 micrograms/kg) significantly increased HCO3- secretion in the presence of indomethacin but had less effect on the impaired HCO3- output caused by HE. In contrast, intravenous infusion of NaHCO3 (3 mmol/kg/hr) ameliorated the acid-base imbalance caused by HE, and significantly restored the impaired HCO3- responses induced by HE but not by indomethacin. Both HE and indomethacin induced extensive damage in the mucosa when the duodenal loop was perfused with 50 mM HCl for 1.5 hr, and these lesions were significantly reduced by NaHCO3 infusion and 16,16-dmPGE2, respectively. These results suggest that HE impaired duodenal HCO3- secretion and reduced the tolerance of the mucosa to acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Effects of NC-1300-B, a new benzimidazole derivative, on hog gastric H+, K+-ATPase, gastric acid secretion and HCl.ethanol-induced gastric lesions in rats.

This study was designed to determine the effect of a newly synthesized benzimidazole derivative NC-1300-B on H+, K+-ATPase (proton pump) in the hog gastric mucosa and on the basal gastric acid secretion and necrotizing agent-induced gastric lesions in rats. NC-1300-B inhibited the proton pump in a concentration-dependent manner and concentrations which inhibited the enzyme activity by 50% were 4.4 x 10(-6) M at pH 6.0 and 3.1 x 10(-5) M at pH 7.4. NC-1300-B administered orally or intraperitoneally 0.5 hr before ligating the pylorus inhibited the gastric acid secretion in a dose-dependent manner. The ED50 values (doses which inhibit acid output or lesion formation by 50%) for acid secretion were 11.5 and 11.0 mg/kg with oral and intraperitoneal administration, respectively. The antisecretory effect in a dose of 100 mg/kg persisted for up to 72 hr. NC-1300-B administered orally or intraperitoneally 0.5 hr before HCl.ethanol administration protected against damage of the gastric mucosa in a dose-dependent manner. The ED50 values for lesion formation were 13.3 and 23.0 mg/kg with oral and intraperitoneal administration, respectively. This protection with an oral dose of 100 mg/kg persisted for up to 72 hr. While pretreatment with 5 mg/kg of indomethacin given subcutaneously did not appreciably reverse the NC-1300-B protection, the pretreatment with 10 mg/kg of N-ethylmaleimide given subcutaneously potently reversed the NC-1300-B protection. NC-1300-B administered intragastrically at 30 mg/kg significantly inhibited the amplitude of gastric contraction for 50 min after intragastric administration. These effects of NC-1300-B on gastric secretion and lesion formation are much the same as those of the established proton pump inhibitor omeprazole, except for the short duration of the action of omeprazole (less than 24 hr).

Adenosine Triphosphatases↗

PubMed1988

Pathogenesis of digitoxin-induced duodenal ulcers in pregnant rats. Roles of gastric acid and duodenal alkaline secretion.

Late-stage pregnant rats (day 17) had higher rates of gastric acid secretion (45-55 mu eq/15 min) as compared to nonpregnant and middle-stage pregnant (day 10) rats (20-25 mu eq/15 min). In contrast, basal rates of duodenal alkaline secretion were significantly lower (2-3 mu eq/15 min) in pregnant rats (day 10 and 17) than those in nonpregnant rats (approximately 5 mu eq/15 min), although the duodenal mucosa responded to acid with a significant rise in HCO3- output in these three groups of rats. In pregnant rats (day 17), a single injection of digitoxin, a Na+ K+-ATPase inhibitor (10 mg/kg, subcutaneously), had no effect on basal acid and alkaline secretions, but significantly blocked the acid-induced HCO3- secretion for more than 18 hr from 6 hr after administration. This drug, when given once daily for four days (10 mg/kg, subcutaneously), produced well-defined ulcers in the proximal duodenum with few lesions in the stomach of female rats, and the severity and incidence were significantly higher in late-stage pregnant rats than in the other two groups of rats. Following repeated administration of digitoxin (10 mg/kg) to late-stage pregnant rats (days 17-20), acid secretion significantly declined after two days of treatment, while the acid-induced HCO3- secretion was significantly attenuated after one day of treatment and remained inhibited during the whole period. These results suggest that an impairment of the mechanisms related to acid-induced HCO3- secretion may be associated with the induction of duodenal ulcers caused by digitoxin in female rats, and the high incidence of these ulcers in late-stage pregnant rats may be due to acid hypersecretion.

Animals↗

PubMed1988

Damage of the peripheral auditory system after operations in the cerebellopontine angle. A scanning electron-microscopic observation in dogs.

Cochlear nerve injuries caused by manipulations in the cerebellopontine angle were electrophysiologically and morphologically investigated in dogs. Operative procedures similar to those performed in the cerebellopontine angle of humans were applied in dogs. Auditory-evoked potentials were recorded throughout the experiments. Postoperatively, the temporal bones were studied with a scanning electron microscope. The portions of the cochlear nerve fibers and branches of the internal auditory artery that exit from the bony cochlea into the internal auditory canal were susceptible to traction force derived from manipulations in the cerebellopontine angle. The cochlear nerve fibers from the basal turn of the cochlea were most easily pulled out from the fundus of the internal auditory canal. In some cases, massive hemorrhages and exudation of plasma were observed in the entire modiolus; these compressed the cochlear nerve trunk. The Schwann-glial junctions of the cochlear nerves were separated in some dogs, indicating this junction was one of the most vulnerable sites to operative manipulations in the cerebellopontine angle.

Animals↗

PubMed1988

Microtubule dynamics in nerve cells: analysis using microinjection of biotinylated tubulin into PC12 cells.

To study microtubule (MT) dynamics in nerve cells, we microinjected biotin-labeled tubulin into the cell body of chemically fused and differentiated PC12 cells and performed the immunofluorescence or immunogold procedure using an anti-biotin antibody followed by secondary antibodies coupled to fluorescent dye or colloidal gold. Incorporation of labeled subunits into the cytoskeleton of neurites was observed within minutes after microinjection. Serial electron microscopic reconstruction revealed that existing MTs in PC12 neurites incorporated labeled subunits mainly at their distal ends and the elongation rate of labeled segments was estimated to be less than 0.3 micron/min. Overall organization of MTs in the nerve cells was different from that in undifferentiated cells such as fibroblasts. Namely, we have not identified any MT-organizing centers from which labeled MTs are emanating in the cell bodies of the injected cells. Stereo electron microscopy revealed that some fully labeled segments seemed to start in the close vicinity of electron dense material within the neurites. This suggests new nucleation off some structures in the neurites. We have also studied the overall pattern of the incorporation of labeled subunits which extended progressively from the proximal part of the neurites toward their tips. To characterize the mechanism of tubulin incorporation, we have measured mean density of gold labeling per unit length of labeled segments at different parts of the neurites. The results indicate access of free tubulin subunits into the neurites and local incorporation into the neurite cytoskeleton. Our results lead to the conclusion that MTs are not static polymers but dynamic structures that continue to elongate even within the differentiated nerve cell processes.

Adrenal Gland Neoplasms↗

PubMed1988

Tau proteins: the molecular structure and mode of binding on microtubules.

Tau is a family of closely related proteins (55,000-62,000 mol wt) which are contained in the nerve cells and copolymerize with tubulin to induce the formation of microtubules in vitro. All information so far has indicated that tau is closely apposed to the microtubule lattice, and there was no indication of domains projecting from the microtubule polymer lattice. We have studied the molecular structure of the tau factor and its mode of binding on microtubules using the quick-freeze, deep-etch method (QF.DE) and low angle rotary shadowing technique. Phosphocellulose column-purified tubulin from porcine brain was polymerized with tau and the centrifuged pellets were processed by QF.DE. We observed periodic armlike elements (18.7 +/- 4.8 nm long) projecting from the microtubule surface. Most of the projections appeared to cross-link adjacent microtubules. We measured the longitudinal periodicity of tau projections on the microtubules and found it to match the 6-dimer pattern better than the 12-dimer pattern. The stoichiometry of tau versus tubulin in preparations of tau saturated microtubules was 1:approximately 5.0 (molar ratio). Tau molecules adsorbed on mica took on rodlike forms (56.1 +/- 14.1 nm long). Although both tau and MAP1 are contained in axons, competitive binding studies demonstrated that the binding sites of tau and MAP1A on the microtubule surfaces are most distinct, although they may partially overlap.

Animals↗

PubMed1988

Gastric surface epithelial cell damage induced by restraint and water-immersion stress in rats. Protective effects of 16,16-dimethyl-prostaglandin E2.

The time course of gastric mucosal surface epithelial cell damage and macroscopically visible lesions in response to restraint and water-immersion stress (22 degrees C) in rats was examined, and the prophylactic effects on it of 16,16-dimethyl-prostaglandin E2 (dmPGE2) were compared with those of papaverine, timoprazole, and atropine. The stress produced surface epithelial cell damage prior to visible lesion, the former increasing in severity with time and reaching a plateau 60 min later, by which time exfoliation of surface epithelial cells was observable along the mucosal folds. In contrast, macroscopically visible lesions appeared 2 h after stress, and severity continued to increase with time. Pretreatment injections (s.c.) of dmPGE2 (3 and 30 micrograms/kg), papaverine (100 mg/kg), and atropine (1 mg/kg) protected the surface cells against stress-induced (1 h) damage, and inhibited visible lesion formation after 4 h stress. Timoprazole (30 mg/kg s.c.) did not protect the surface cells, but did markedly inhibit visible lesion formation. DmPGE2, papaverine, and atropine, but not timoprazole, inhibited stress-induced increases in gastric contractions. DmPGE2, timoprazole, and atropine, but not papaverine, inhibited acid secretion in stress conditions. These results indicated that stress induced damage to the gastric mucosa within 1 h due to increased gastric contractions, and the surface epithelial cell damage developed into macroscopically visible lesions in the presence of acid, and that dmPGE2 protected the surface epithelium against stress-induced damage probably by inhibiting gastric contractions.

16,16-Dimethylprostaglandin E2↗

PubMed1988

Duodenal ulcers induced by indomethacin plus histamine in the dog. Involvement of the impaired duodenal alkaline secretion in their pathogenesis.

Mongrel dogs of either sex, weighing 14.0 +/- 0.7 kg, were given indomethacin orally in a dose of 70 mg/dog, and they were deprived of food thereafter. Twelve hours later, the animals were given histamine-2HCl intramuscularly 4 times every hour in a dose of 40 or 80 micrograms/kg. Indomethacin followed by histamine treatment produced well-defined ulcers in the proximal duodenum within 18 h with a few lesions in the stomach, although either of these agents alone did not induce any damage in the mucosa. Both the severity and incidence of the duodenal lesions were increased dose-dependently by histamine; the lesion index was 38.8 +/- 8.4 mm2 (n = 7) with an incidence of 100% at the dose of 80 micrograms/kg of histamine. The duodenal lesions mostly consisted of 2-4 round or elongated lesions which penetrated to the muscularis mucosae in some cases (42.8%). Histamine caused a marked increase in acid secretion in dogs with a vagally innervated total pouch, while indomethacin significantly inhibited the increased alkaline secretion caused by acid (50 mM HCl for 10 min) in the duodenal pouch (10 cm distal to the pylorus). Both cimetidine (20 mg/kg) and 16,16-dimethyl prostaglandin E2 (3 micrograms/kg), given subcutaneously, prevented these lesions in the duodenum as well as in the stomach by inhibiting acid secretion and/or increasing duodenal alkaline secretion. These results suggest that (a) indomethacin consistently produced ulcers in the duodenum of the dog when acid hypersecretion was induced by histamine, and (b) an impaired duodenal alkaline secretion may be an important pathogenetic element in this model.

Acid-Base Equilibrium↗

PubMed1988

Repair of mucosal damage induced by ethanol in the rat stomach. Effects of concentration, exposure period and prostaglandins.

We investigated the relationship between the severity of acute injury and the rapidity of mucosal repair in stomachs of anesthetized rats, and examined the influence of prostaglandins (PGs) on the process of restoration. Different degrees of mucosal damage were produced using ethanol and by varying the concentration (5-100%) and the exposure period (1-60 min). Exposure of the stomach for 10 min to ethanol induced hemorrhagic lesions and a reduction in the transmucosal potential difference (PD); its severity and its magnitude were increased in a concentration-related manner. After removal of ethanol, the reduced PD recovered quickly in the case of 5-25% ethanol, but it normalized slowly or did not show any recovery in the case of 50 or 100% ethanol, respectively. Histologically, ethanol at 5-25% produced various degrees of damage in the superficial epithelial cells, while the damage was deeper into the mucosa beyond the basal lamina after exposure to ethanol at 50% or greater. Similar phenomena were observed after exposure to 50% ethanol for various periods; the rapidity of PD recovery and mucosal restoration was faster when the exposure period was less than 2 min, and these parameters became slower as it was increased. Moreover, the PD recovery was significantly expedited or delayed, respectively, by 16,16-dimethyl PGE2 (30 micrograms/kg) or indomethacin (5 mg/kg), and the former counteracted the inhibitory effect of indomethacin. These results suggest that the process of mucosal regeneration may largely depend on the severity of damage initially formed, and probably involves factors sensitive to endogenous PGs.

Administration, Cutaneous↗

PubMed1988

Huge pelvic fibromatosis encroaching on the urinary bladder. A case report.

A patient with a huge pelvic fibromatosis, a form of intra-abdominal desmoid, encroaching on the urinary bladder is described. Because of its rarity, there is frequently a lack of diagnostic awareness of this tumor, particularly in the gynecological or urological patient. Although this tumor is a locally invasive benign tumor which dose not metastasize, management by radical tumor excision without the sacrifice of the major pelvic nerves and vessels is mandatory, since this tumor has generally a high postsurgical recurrence rate.

Adult↗

PubMed1988

Dissolution of antisecretory and cytoprotective action of PGE2 in rats.

Oral administration of 60% ethanol in 150 mM HCl (HCl.ethanol) to rats produced gastric mucosal lesions within 1 hr. PGE2 given s.c. at 0.1 to 3 mg/kg 0.5 hr before HCl.ethanol significantly prevented the lesion formation. The protection afforded with 3 mg/kg of PGE2 persisted for 6 or 12 hr after administration. PGE2 given s.c. at 3 mg/kg significantly inhibited gastric secretion in pylorus-ligated and intact rats, but the action disappeared 6 hr later.

Animals↗

PubMed1988

Effects of topical application of acidified omeprazole on acid secretion and transmucosal potential difference in anesthetized rat stomachs.

Effects of topical application of omeprazole on transmucosal potential difference (PD), luminal pH and histamine-stimulated acid secretion were examined in anesthetized rat stomachs, and they were compared with those of systemic administration. Omeprazole was suspended in 1% CMC with NaHCO3 (pH 9.0) or dissolved in 0.1 N HCl (pH 1.0). Both omeprazole (30 mg/kg, pH 9.0) and cimetidine (100 mg/kg), given i.d., increased the pH and inhibited acid secretion induced by histamine (8 mg/kg/hr, i.v.), while basal gastric PD was markedly elevated only by the former. Similar responses in PD, pH and acid output were obtained dose-dependently after brief exposure of the stomach (10 min) to omeprazole (0.3-30 mg/kg), even in acidic conditions, but the effects of acidified omeprazole disappeared depending upon the latency period in 0.1 N HCl; there was no effect when applied at more than 30 min after dissolution. Of interest, subsequent exposure of the stomach to a mercaptane compound (cysteine, 100 mg/kg) for 30 min significantly reversed the antisecretory effect of omeprazole (both i.d. and i.g.) but not of cimetidine. These results suggest that omeprazole has a local antisecretory action even in acidic stomachs, probably through an inhibition of the H+/K+ATPase activity, and the increase of PD caused by omeprazole may be a characteristic phenomenon seen after the blockade of H+/K+ ATPase, but is not associated with acid inhibition itself.

Administration, Cutaneous↗