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Biomedical subjects

M Moriga

Publications and source records attributed to M Moriga.

At least 19 recordsLinked to original sources
PubMed1999

Central effects of pituitary adenylate cyclase activating polypeptide (PACAP) on gastric motility and emptying in rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the secretin-glucagon-vasoactive intestinal peptide (VIP) peptide family. PACAP is widely distributed not only in the mammalian brain but also in the gastrointestinal tract. Here, we investigated the effects of central and peripheral administrations of PACAP on gastric motility and gastric emptying in rats. We found that the intracerebroventricular or intracisternal injection of PACAP increased gastric motility in a dose-dependent manner. The intracisternal injection of PACAP delayed gastric emptying. These central effects of PACAP on gastric motility and emptying were blocked by bilateral vagotomy. In contrast, intravenous administration of PACAP decreased gastric motility and delayed gastric emptying. The peripheral inhibitory effect was unaffected by bilateral vagotomy, adrenalectomy, phentolamine, and propranolol. We investigated the effect of PACAP38 on blood glucose levels (BGL) at the same doses as those used in the gastric motility and emptying studies in urethane-anesthetized rats. The intravenous but not intracerebroventricular injection of PACAP38 (1-8 nmol/rat) produced a significant increase in the BGL. We conclude that PACAP has opposite central and peripheral effects on gastric motility, ie, central PACAP activates the vagal pathway in the central nervous system to increase gastric motility, whereas peripheral PACAP inhibits gastric motility via an unknown pathway. The delay in gastric emptying after the central administration of PACAP might be due to the lack of coordinated gastropyloroduodenal contraction, whereas that after the peripheral administration might be due to the inhibition of gastric contraction, and this effect may be related to the hyperglycemic action of PACAP.

Adrenalectomy↗
PubMed1997

Central administration of PACAP stimulates gastric secretion mediated through the vagal pathway in anesthetized rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide that was originally isolated from ovine hypothalamic tissue. The peptide has two amidated forms, PACAP38 and PACAP27. In this study, we examined the effects of centrally administered PACAP38 and PACAP27 on gastric secretion in anesthetized rats. Centrally administered PACAP stimulated gastric acid and pepsin secretion in a dose-dependent manner. PACAP38 was 1.5-2 times more potent than PACAP27 on gastric secretion. By contrast, intravenously administered PACAP38 had no effect on basal or pentagastrin-stimulated gastric secretion. PACAP6-38, a PACAP antagonist, by itself at high doses also stimulated gastric and pepsin secretion, but at lower doses had no effect. Centrally administered PACAP6-38 at a dose that had no effect on gastric secretion, atropine pretreatment, or vagotomy pretreatment, suppressed the stimulatory effect of PACAP38. It is concluded that centrally administered PACAP may have a regulatory effect on gastric secretion through PACAP receptors and the vagal pathway.

Anesthesia↗
PubMed1995

[Effects of centrally administered NPY on stress induced gastric ulcers in the rat].

We investigated the central effects of neuropeptide Y (NPY) on stress-induced gastric ulcers in water immersion rats. Intracisternally administered NPY dose-dependently aggravated, but intravenously administered NPY did not affect stress ulcers in rats. Intraperitoneal pre-treatment of atropine completely blocked the central effect of NPY, but neither pyrilamine nor cimetidine affected. Intracisternal administration of NPY aggravated stress ulcers not through histamine mediated mechanism but by parasympathetic pathway. It is suggested that centrally administered NPY acted by the inhibition on gastric motility and by the suppression on gastric mucosal blood flow rather than by the stimulation on gastric secretion in rats.

Animals↗
PubMed1993

Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat.

Neuropeptide Y is distributed abundantly not only in the brain, but also in the gastrointestinal tract and suppresses intestinal muscle contraction in isolated muscle preparations. The purpose of the present study was to determine whether centrally administered neuropeptide Y modulated gastric emptying and intestinal transit in conscious rats. Graded doses of neuropeptide Y were administered intracisternally 1 min before ingestion of test meals through an oral tube. Four hours after ingestion of 60 Amberlite pellets, the rats were sacrificed and residual pellets in the stomach and the small intestine segments were counted to calculate the solid meal transit rate. The liquid meal transit rate was calculated 1 hr after 0.07% phenol red ingestion by determining the residual phenol red in the stomach and the small intestine segments. Neuropeptide Y elicited potent suppression of gastric emptying and intestinal transit of both solid and liquid meals. Pretreatment with propranolol antagonized, whereas phentolamine did not affect, the suppressive effect of central neuropeptide Y. Although carbachol blocked the effects of neuropeptide Y, neither atropine nor hexamethonium altered the actions of neuropeptide Y. In conclusion, centrally administered neuropeptide Y strongly inhibited gastrointestinal transit by stimulating a beta-adrenergic pathway.

Animals↗
PubMed1991

Centrally administered NPY stimulated gastric acid and pepsin secretion by a vagally mediated mechanism.

We investigated the possible roles of centrally administered neuropeptide Y (NPY) on gastric secretion, serum gastrin levels and gastric mucosal blood flow in anesthetized rats. Centrally administered NPY dose-dependently stimulated gastric acid and pepsin secretion. The stimulatory effect of intracerebroventricular administration of NPY was more potent than that of intracisternal administration. Centrally administered NPY also increased gastric secretion in the central noradrenaline depleted rats. In contrast, intravenously administered NPY had no influence on gastric secretion. These stimulatory effects were abolished by vagotomy or atropine pretreatment. The serum gastrin levels did not change after central NPY injection. Although intravenously administered NPY slightly increased gastric mucosal blood flow, centrally administered NPY slightly diminished gastric mucosal blood flow. These results indicate that centrally administered NPY markedly influences gastric functions in the rat.

Animals↗
PubMed1989

Effects of 15(S)-15-methyl prostaglandin E2 methyl ester on phospholipid metabolism in rat gastric mucosa.

The effects of 15(S)-15-methyl prostaglandin E2 (PGE2) methyl ester on gastric mucosal metabolism of phospholipids in intact rats and rats injured by intragastric instillation of acidified taurocholic acid were examined by using radioisotope-labeled precursors. The incorporation of palmitic, oleic and arachidonic acids into phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was reduced by treatment with 15(S)-15-methyl PGE2 methyl ester in the intact rats, but the incorporation of glycerol was unaffected or affected only slightly. Instillation of acidified taurocholic acid resulted in decreased incorporation of palmitic acid and glycerol into PC and PE, whereas pretreatment with 15(S)-15-methyl PGE2 methyl ester caused the incorporations of these precursors to be maintained after acidified taurocholic acid treatment. These results suggest that 15(S)-15-methyl PGE2 methyl ester may reduce the incorporation of fatty acids into PC and PE by inhibition of the deacylation-reacylation cycle either directly or indirectly, whereas acidified taurocholic acid decreases de novo synthesis of PC and PE, and probably also the reacylation of fatty acid into phospholipids. Pretreatment with 15(S)-15-methyl PGE2 methyl ester protected the PC- and PE-synthesizing activity against the injury induced by acidified taurocholic acid, and this effect may be involved in the prevention of mucosal damage.

Animals↗
PubMed1989

Inhibitory action of enprostil (4,5-dehydro-16-phenoxy-17,18,19,20-tetranor-PGE2) on tetra-gastrin stimulated acid secretion in human subjects.

A double-blind study was conducted to examine the effect of enprostil on tetra-gastrin stimulated gastric acid secretion in twelve healthy male volunteers. Each subject underwent four tests in random order on separate days with oral doses of 15, 25, 35 micrograms enprostil and placebo. After measuring basal secretion and gastrin release, tetra-gastrin was injected intramuscularly. Gastric secretion and gastrin release were measured over the next two hours. Enprostil dose-dependently inhibited tetragastrin stimulated gastric secretion volume, acid and pepsin output. There were significant differences in gastric acid secretion inhibition between the 15 and 25 micrograms doses, and the 15 and 35 micrograms doses, but only a slight dose response was seen between the 25 and 35 micrograms doses with no significant difference. Serum gastrin level was not influenced by the administration of enprostil. No side effects attributed to enprostil were observed throughout the study.

Adult↗
PubMed1988

Protection against alcohol-induced gastric mucosal injury by geranylgeranylacetone: effect of indomethacin.

The mechanism of gastric mucosal protection by an antiulcer agent, geranylgeranylacetone (GGA), against ethanol-induced injury was investigated. The experiments were conducted with groups of rats with and without intraperitoneal indomethacin pretreatment. Animals received intragastrically either a dose of GGA (200 mg/kg) or a vehicle, followed 30 min later by 1 ml of absolute ethanol. The rats were sacrificed after 30 min and the gastric mucosa was subjected to macroscopic and histologic assessment and the measurements of adherent mucus, its dimension and chemical composition. In the absence of GGA, ethanol produced advanced macroscopic necrosis (greater than 38%) and the extensive necrotic lesions were visible upon histologic examination. Pretreatment with GGA significantly reduced (p less than 0.001) the extent and depth of mucosal necrotic lesions caused by ethanol, and this protection was not thwarted by indomethacin. Evaluation of the adherent mucus and its dimension by Alcian blue uptake and inverted microscope technique revealed that GGA was also capable of preventing the untoward effect of indomethacin on the adherent gastric mucus gel and its thickness. Results of chemical analyses established that in the absence of GGA indomethacin caused an increase in mucus protein (15%) and a decrease in its covalently bound fatty acids (67%) and lipids (36%). The decrease in lipids was particularly reflected in the content of phospholipids. Indomethacin, however, had no apparent effect on the composition of gastric mucus elaborated in the presence of GGA. The results suggest that gastric mucosal protective action of GGA is not mediated by endogenous prostaglandins but rather appears to involve the metabolism of mucosal lipids.

Animals↗
PubMed1987

Enhancement of the lipid content and physical properties of gastric mucus by geranylgeranylacetone.

The effects of intragastric administration of geranylgeranylacetone (GGA) on the content, composition and physical properties of the mucus component of the gastric mucosal barrier were investigated. One group of rats received twice daily for 3 consecutive days a dose of 100 mg/kg body weight of GGA, while the control group was subjected to daily doses of the vehicle. Sixteen hours following the last dose, the animals were killed, and their stomach was cut open and subjected to measurements of the adherent mucus gel content, analysis of its lipids and molecular forms of elaborated mucin, and evaluation of the viscosity and H+ retardation capacity. The results revealed that GGA elicited a 62% increase in the adherent mucus gel and caused a marked decrease in the proportion of the lower molecular weight mucin. Furthermore, the mucus of the GGA group exhibited a 67% higher content of covalently bound fatty acids and contained 46% more total lipids which were greatly (143%) enriched in phospholipids. The physical measurements demonstrated that mucus elaborated in the presence of GGA also exhibited 2.3 times higher viscosity and had a 32% greater ability to retard the diffusion of H+ than the mucus of the control group. The results suggest that GGA exerts a profound effect on the lipid content and the properties of gastric mucus associated with the maintenance of the mucosal integrity.

Animals↗
PubMed1987

Effects of taurocholic acid/HCl alone or after pretreatment with geranylgeranylacetone on phospholipid metabolism in rat gastric mucosa.

Changes in phospholipid metabolism in gastric mucosa caused by instillation of taurocholic acid (TCA)/HCl (80 mM/300 mM) into the stomach of rats and the effects of pretreatment with an antiulcer agent, geranylgeranylacetone (GGA), were studied after intravenous injection of radioisotope-labeled precursors. The instillation of TCA/HCl rapidly reduced the incorporation of labeled fatty acids and glycerol into phosphatidylcholine and phosphatidylethanolamine, indicating the inhibition of de novo synthesis of phospholipids. These changes were restored by 120-150 min after the TCA/HCl treatment. Pretreatment with GGA enhanced the incorporation of precursors into phosphatidylcholine immediately after the instillation of TCA/HCl. Experiments in which the mucosal lipids were labeled with fatty acids prior to the instillation of TCA/HCl showed that the degradation of cellular lipids and release of the products into the gastric lumen were induced by TCA/HCl and that these changes were not prevented by GGA. Since GGA almost completely inhibited the gastric lesions induced by TCA/HCl, the enhancement of synthesis of mucosal phosphatidylcholine induced by GGA may be involved in the prevention of gastric damage. The incorporation of labeled fatty acids into free fatty acid fraction and diacylglycerol was increased quickly by the TCA/HCl treatment, suggesting early damage to the blood vessels of the gastric mucosa; these changes were inhibited significantly by GGA.

Animals↗
PubMed1987

Effects of ethanol alone or after pretreatment with 20% ethanol on phospholipid metabolism in rat gastric mucosa.

Changes in phospholipid metabolism in gastric mucosa caused by instillation of absolute ethanol (a cell-damaging agent) into the stomach of rats and the effects of pretreatment with 20% ethanol (a mild irritant) were investigated by using radioisotope-labeled fatty acids and glycerol. The labeled precursors were incorporated mainly into phosphatidylcholine and triacylglycerol, and also to lesser extents into phosphatidylethanolamine and phosphatidylinositol + phosphatidylserine. The instillation of absolute ethanol reduced the incorporation of fatty acids and glycerol into phospholipids within 15 min, indicating the inhibition by ethanol of de novo synthesis of phospholipids. Pretreatment with 20% ethanol caused the incorporation of fatty acids into phospholipids to be maintained after absolute ethanol instillation. These results suggest that the pretreatment with 20% ethanol may protect the cellular synthetic activity of phospholipids against damage by absolute ethanol. The incorporation of fatty acids into the free fatty acid fraction, monoacylglycerol and diacylglycerol was increased by absolute ethanol instillation, suggesting damage to the blood vessels of the gastric mucosa, and these changes were inhibited to some extent by the pretreatment with 20% ethanol.

Animals↗
PubMed1987

Distribution of gastrin-releasing peptide (GRP)-like immunoreactivity in the rat.

Rat tissues were examined for gastrin-releasing peptide (GRP)-like immunoreactivity, using carboxy-terminus-specific antibody made against GRP (19-27), which is thought to be the biologically active site and to be common among species. The distribution of GRP-like immunoreactivity in the rat was similar to that of bombesin-like immunoreactivity. Sephadex G 50 chromatography revealed two peaks of GRP-like reactivity in the rat stomach. Immunohistochemical studies using the antiserum to GRP (19-27) revealed numerous nerve fibers in the mucosa of the rat stomach. In the antral mucosa, GRP-containing nerves were present mainly around the base of the antral glands. Some GRP-containing nerves were in contact with gastrin-containing cells and somatostatin-containing cells. GRP-containing nerve fibers were numerous in the middle portion of the oxyntic gland, where somatostatin-containing cells were also detected. None of the endocrine cells stained positively with anti-GRP serum. These results support the hypothesis that GRP is a neurotransmitter in the stomach and that the peptide plays a physiological role in the gastrointestinal tract.

Animals↗
PubMed1987

Effects of anti-GRP gamma-globulin on gastrin release and gastric secretion in the rat: evidence for the physiologic role of endogenous GRP in the regulation of gastric function.

To assess the effects of endogenous GRP on vagal gastrin release and acid secretion, anti-GRP gamma-globulin was infused in anesthetized rats to bind endogenously released GRP. Anti-GRP gamma-globulin blocked the gastrin-releasing effects caused by 4 micrograms/kg/hr of exogenous GRP infusion and suppressed gastrin release by electrical vagal stimulation. In spite of this suppression, anti-GRP gamma-globulin did not alter basal or vagal-stimulated acid secretion.

Animals↗
PubMed1986

Paradoxical effects of gastrin releasing peptide on gastrin release and gastric secretion in the rat.

The effects of gastrin releasing peptide (GRP) on gastrin release and gastric secretion were studied in anesthetized rats. Intravenous infusion of GRP (1-16 micrograms/kg/hr) caused a dose-dependent increase in serum gastrin level, however, it had no effect on basal gastric secretion in the lumen-perfused stomach preparation. Furthermore, GRP inhibited gastric secretion stimulated by pentagastrin or histamine dose-dependently, but not by carbachol. Simultaneous infusion of GRP and a beta adrenergic blocking agent, propranolol, an inhibitor of somatostatin release, did not alter the inhibitory effect of GRP on pentagastrin-stimulated gastric secretion. These results suggest that the inhibitory effect of GRP on gastric secretion in a stimulated condition is mediated via peptide hormones coreleased by GRP, and not via beta-adrenergic pathways.

Animals↗
PubMed1986

Cholinergic effects of histamine-H2 receptor antagonists partly through inhibition of acetylcholinesterase.

The effects of histamine H2-receptor antagonists on acetylcholinesterase and pseudocholinesterase activity were studied. All H2-antagonists tested inhibited both enzyme activities dose-dependently. The potency of inhibitory activity of H2-antagonists on acetylcholinesterase estimated from median inhibitory dose were in the following order of decreasing activity: ranitidine greater than TZU-0460 greater than cimetidine greater than YM-11170, whereas that on pseudocholinesterase were TZU-0460 greater than ranitidine greater than cimetidine greater than YM-11170. As the effects derived from the inhibition of acetylcholinesterase by H2-antagonists may affect intestinal motility, we studied ileal muscle contractions. Ranitidine had the most potent stimulating effect on contraction, the pattern of which was similar to physostigmine and was blocked by atropine and morphine. YM-11170 had a weak action on muscle contraction and cholinesterase activities.

Animals↗