Motoyuki Moriga

Contact Electrode Method in Hydrogen Gas Clearance Technique: A New Method for Determination of Regional Gastric Mucosal Blood Flow in Animals and Humans

A method was developed that was capable of measuring regional gastric mucosal blood flow in animals and humans. The method is based on the clearance of hydrogen gas from mucosal tissue as measured by a newly devised electrode that is placed in contact with gastric mucosa. The structure of the electrode was such that an insulated platinum spring with a tapered active tip was attached to a lead of suitable flexibility and rigidity. The method yielded reliable values of regional gastric mucosal blood flow, 93.5 ± 26.4 and 52.7 ± 16.1 ml/min · 100 g (mean ± SD) in the antrum and corpus of the glandular stomach of anesthetized rats respectively. Desaturation of hydrogen gas was monoexponential by our method, whereas it was multiexponential in most cases when a commercially available wire electrode was inserted through the mucosal layer. Some hydrogen gas escape into the gastric lumen was observed causing an overestimation of regional gastric mucosal blood flow when the stomach was inflated with air (10.5 ± 8.9 ml/min·100 g) or perfused (3.6 ± 2.9 ml/min 100 g, mean ± SD). Regression analysis demonstrated a highly significant linear correlation between aminopyrine clearance and blood flow measured by the contact electrode method in the pentagastrin stimulated state (r = 0.935, p

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.

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.

Urotensin II-immunoreactive neurons in the caudal neurosecretory system of freshwater and seawater fish

SummaryAntiserum generated against synthetic urotensin II of the goby, Gillichthys mirabilis, was used to localize urotensin II in the caudal neurosecretory system in six species of freshwater teleosts; Cyprinus carpio, Carassius auratus, Oreochromis mossambicus, Oreochromis niloticus, Salmo gairdneri and Plecoglossus altivelis, and six species of seawater teleosts: Acanthogobius flavimanus, Pagrus major, Paapristipoma trilineatum, Trachurus japonicus, Seriola dumerili and Seriola quinqueradiata. In the carp, urotensin II-immunoreactive perikarya were classified into three groups according to their size and shape. Small cells were located in the spinal cord dorsal to the urophysis, medium-sized cells immediately anterior to the urophysis, and large cells anterior to the medium-sized cells. In each group, a small number of nonreactive cells was found. Urotensin II-immunoreactive nerve fibers extended toward the urophysis and terminated around the blood vessels. Other species of teleosts showed a similar immunoreaction to that observed in the carp. The immunoreaction of the urophysis was stronger in seawater fish than freshwater fish. Urotensin II-immunoreactive elements could not be detected in the brains of the carp, goldfish and goby.

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 conclusions, centrally administered neuropeptide Y strongly inhibited gastrointestinal transit by stimulating a beta-adrenergic pathway.

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.

Central Administration of PACAP Stimulates Gastric Secretion Mediated Through the Vagal Pathway in Anesthetized Rats

Pituitary adenylate cyclase activatingpolypeptide (PACAP) is a neuropeptide that wasoriginally isolated from ovine hypothalamic tissue. Thepeptide has two amidated forms, PACAP38 and PACAP27. Inthis study, we examined the effects of centrallyadministered PACAP38 and PACAP27 on gastric secretion inanesthetized rats. Centrally administered PACAPstimulated gastric acid and pepsin secretion in adose-dependent manner. PACAP38 was 1.5-2 times more potentthan PACAP27 on gastric secretion. By contrast,intravenously administered PACAP38 had no effect onbasal or pentagastrin-stimulated gastric secretion.PACAP6-38, a PACAP antagonist, by itself at high dosesalso stimulated gastric and pepsin secretion, but atlower doses had no effect. Centrally administeredPACAP6-38 at a dose that had no effect on gastricsecretion, atropine pretreatment, or vagotomypretreatment, suppressed the stimulatory effect ofPACAP38. It is concluded that centrally administeredPACAP may have a regulatory effect on gastric secretionthrough PACAP receptors and the vagalpathway.

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

SummaryThe 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 > TZU-0460 > cimetidine > YM-11170, whereas that on pseudocholinesterase were TZU-0460 > ranitidine > cimetidine > 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.

Effect of teprenone on the content of phospholipids in gastric secretion in man

SummaryThe phospholipid content of basal and pentagastrin-stimulated gastric secretion was measured in 9 healthy volunteers. One week oral administration of teprenone did not alter the gastric acid and pepsin secretion. The phospholipid content was increased by teprenone. Changes in subclasses of phospholipids in gastric mucus by teprenone treatment, namely, increased phosphatidylcholine and decreased lysophosphatidylcholine, were observed.

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

Pituitary adenylate cyclase activatingpolypeptide (PACAP) is a new member of thesecretinglucagon-vasoactive intestinal peptide (VIP)peptide family. PACAP is widely distributed not only inthe mammalian brain but also in the gastrointestinal tract.Here, we investigated the effects of central andperipheral administrations of PACAP on gastric motilityand gastric emptying in rats. We found that theintracerebroventricular or intracisternal injection of PACAP increasedgastric motility in a dose-dependent manner. Theintracisternal injection of PACAP delayed gastricemptying. These central effects of PACAP on gastricmotility and emptying were blocked by bilateralvagotomy. In contrast, intravenous administration ofPACAP decreased gastric motility and delayed gastricemptying. The peripheral inhibitory effect wasunaffected by bilateral vagotomy, adrenalectomy,phentolamine, and propranolol. We investigated theeffect of PACAP38 on blood glucose levels (BGL) at thesame doses as those used in the gastric motility andemptying studies in urethane-anesthetized rats. Theintravenous but not intracerebroventricular injection ofPACAP38 (1-8 nmol/rat) produced a significant increasein the BGL. We conclude that PACAP has opposite central and peripheral effects on gastricmotility, ie, central PACAP activates the vagal pathwayin the central nervous system to increase gastricmotility, whereas peripheral PACAP inhibits gastricmotility via an unknown pathway. The delay in gastricemptying after the central administration of PACAP mightbe due to the lack of coordinated gastropyloroduodenalcontraction, whereas that after the peripheral administration might be due to the inhibitionof gastric contraction, and this effect may be relatedto the hyperglycemic action of PACAP.