Evidence against local neural mechanism for intestinal postprandial hyperemia

The role of local intestinal nerves in the nutrient-induced intestinal hyperemia was investigated in jejunal segments of anesthetized dogs by comparing the hyperemic effect of intraluminal glucose and oleic acid solutions before and after mucosal anesthesia and infusions of methysergide, hexamethonium, and tetrodotoxin. Methysergide, hexamethonium, and tetrodotoxin all failed to alter either the vascular or metabolic responses to luminal placement of glucose or oleic acid. The increases in blood flow and oxygen uptake produced by glucose or oleic acid, however, were blocked or attenuated after exposing the mucosa to dibucaine. The effect was norepinephrine due to an altered vascular response to vasoactive substances as dibucaine did not alter vascular responses to isoproterenol or norepinephrine. Dibucaine, however, inhibited active transport and increased passive transport of glucose across rat intestinal sacs in vitro. Oxygen consumption of the canine jejunal mucosa was also inhibited by dibucaine in vitro. It seems that inhibition of the nutrient-induced intestinal hyperemia by dibucaine is due, at least in part, to its effect on oxygen consumption and glucose transport of the mucosal epithelial cells. Nutrient-induced hyperemia appears not to be neurally mediated but more closely related to metabolism.     

Effect of <Emphasis Type="Italic">Cannabis sativa</Emphasis> extract on gastric acid secretion,oxidative stress and gastric mucosal integrity in rats

Studies were conducted in pylorus-ligated rats to investigate the effect of Cannabis sativa extract on gastric acid secretion, experimental gastric ulcer and on oxidative stress and inflammatory markers in the gastric mucosa. C. sativa (5, 10 and 20 mg/kg, expressed as Δ⁹-tetrahydrocannabinol) was administered subcutaneously daily for 4 weeks prior to pylorus ligation and different treatments. Under basal conditions, pretreatment with cannabis extract at doses of 5 and 10 mg/kg increased gastric acid secretion and induced minimally visible gastric mucosal lesions in the 4 h pylorus-ligated rat. Malondialdehyde and nitric acid concentration increased, while reduced glutathione decreased by cannabis at doses of 5 and 10 mg/kg in gastric mucosa. TNF-α increased by cannabis extract at doses of 5 and 10 mg/kg but decreased following the high dose of 20 mg/kg. On the other hand, the gastric acid secretory responses stimulated by pentagastrin or carbachol (but not histamine) were inhibited in rats pretreated with cannabis extract. Under these conditions, cannabis decreased pepsin content after pentagastrin and carbachol but not histamine stimulation. Cannabis also decreased lipid peroxidation and nitric oxide content, and increased both reduced glutathione and catalase activity in mucosa. Moreover, cannabis decreased mucosal inflammation (level of TNF-α) and the development of gastric mucosal lesions. Cannabis administered for 1 month prior to pylorus-ligation and either acidified aspirin or ethanol (96 %) decreased the development of gastric mucosal damage in a dose-dependent manner, along with reduction in gastric acid output, gastric mucosal oxidative stress and inflammation (TNF-α). Sections of gastric mucosa stained with periodic acid Schiff showed increased mucus secretion by cannabis in basal conditions and after treatment with aspirin or ethanol. Results indicate that: (1) the effect of cannabis differs in basal conditions and after exposure of the gastric mucosa to high acid concentrations or other chemical noxious agents; (2) cannabis administered systemically exerts gastric mucosal protective effects against mucosal damage evoked by stimulation of gastric acid secretion, acidified aspirin or ethanol. These effects of cannabis are likely to involve inhibition of gastric acid and pepsin secretion, increased mucus, decreased oxidative stress and inflammation in gastric mucosa.     

Caveolin-1 immuno-expression in human gastric cancer: histopathogenetic hypotheses

The immunohistochemical expression of caveolin-1 (cav-1) was evaluated in a series of gastric carcinomas (GC) and in the adjacent normal gastric mucosa. Cav-1 immuno-expression was found in most GC (94%) with a significantly higher amount in the Lauren intestinal type in comparison to the diffuse-type carcinomas. Interestingly, gastric intestinal metaplasia as well as the cells at the base and neck of gastric pits within all fundic mucosal fragments showed an evident cav-1 immuno-staining, suggesting a histogenetic derivation of these lesions from the trans-differentiation of chief cells or from a cryptic progenitor population at the base of fundic glands, as recently hypothesized by other authors. The absence of significant correlations between cav-1 immuno-expression and the other clinico-pathological parameters, such as the stage of disease or the patients overall survival, indicates that the role of cav-1 in GC is neither stage-specific nor related to prognosis.     

Induction of colitis in rats by 2-2′-azobis(2-amidinopropane) dihydrochloride

Reactive oxygen metabolites (ROM) may play a role in the pathophysiology of inflammatory bowel disease (IBD) and ischemia-reperfusion-induced intestinal injury. Although there are many reports of intestinal mucosal injury associated with neutrophil-derived ROM, free radicals themselves have not been reported to induce intestinal mucosal injury. We administered intrarectally 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) to rats, an azo compound that generates free radicals in vitro. Acute mucosal injury was assessed histologically by light microscopy and biochemically by myeloperoxidase (MPO) activity. Intrarectal administration of AAPH (60, 90, 150 mg/kg) caused erythema, edema, and histologically verifiable mucosal inflammation. MPO activity was increased 9- to 18-fold above the control level. The levels of thiobarbituric acid (TBA) reactants and sulfhydryls (SH) were significanty (P<0.01) increased and decreased, respectively, by 90 mg/kg AAPH. Sulfasalazine, 5-aminosalicylic acid, the LTB₄ receptor antagonist SC-41930, and the antioxidant glutathione prevented the inflammation. This model of mucosal inflammation may be useful in evaluating new therapeutic agents for the treatment of IBD.     

Data to the intracellular effects of prostacyclin in rat gastric mucosa

Using specific radioimmunoassay it seems that Prostacyclin has a strong effect on the cyclic nucleotide-content of the rat gastric antral mucosa. Shortly (1 min) after an intragastric application of 100 g/kg Prostacyclin the cAMP and the cGMP-content showed a significant decrease.Investigating the antral and fundic mucosal calmodulin-levels, it seems that 15–30 mins after Prostacyclin application both tend to increase.It seems very probable that the primary intracellular effect of Prostacyclin in the gastric mucosa is directed to the so-called second messenger system but later Prostacyclin activates the calmodulin-system too.     

Clinicopathological features of duodenal bulb biopsies and their relationship with upper gastrointestinal diseases

AimTo assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection.MethodsClinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively.ResultsA total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia.Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps.Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps.There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection.ConclusionsThe mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.     

Adenylate cyclase in human gastric mucosa: its activation by histamine in morphologically different biopsy specimens

Summary In morphologically different biopsy specimens from fundic, antral and duodenal mucosa of 134 persons, basal and histamine stimulated adenylate cyclase activity was studied: Basal and stimulated adenylate cyclase activities were log-normally distributed. Only in the fundic but not in the antral and duodenal mucosa adenylate cyclase was sensitive to histamine. The mean basal activity in the fundic gastric mucosa was 148, in response to 10^–5 mol/l histamine 292 pmol cAMP/mg protein/20 min. In human fundic biopsy specimens histologically identified as normal gastric mucosa, the stimulatory effect of histamine on adenylate cyclase decreased with the individual's age. In bioptic material from patients suffering from histologically proven chronic gastritis the histamine effect decreased with the degree of atrophy. A similar loss of histamine sensitivity was found in gastric mucosal biopsies of antrectomized individuals operated at least 5 years before by the Billroth I or II method, whereas in the mucosa of patients with gastric or duodenal ulcer no loss occurred. In contrast, the most pronounced stimulatory action of histamine was found in this latter group. Since a histamine sensitive adenylate cyclase is localized only in the glandular area of the fundic mucosa and the histamine sensitivity depends on a morphological intact structure of the mucosa, it can be concluded, that the effects of histamine on adenylate cyclase and on hydrochloric acid secretion have to be considered as a mechanism linked together.This study was supported by a grant from the Deutsche Forschungsgemeinschaft     

Molecular genetics of the human Na+/glucose cotransporter

Summary Recent success in expression cloning has revealed the primary structure of the Na⁺/glucose cotransporter from rabbit small intestine, and this has subsequently led to the cloning of the Na⁺/glucose cotransporters from human small intestine and human kidney. Close homology is evident between the rabbit and human intestinal Na⁺/glucose cotransporters at the DNA level, and the predicted amino acid and secondary structure levels. The Na⁺/glucose cotransporter amino acid sequence from human kidney is 57% identical with that from human small intestine. Significant homology also exists between these Na⁺/glucose cotransporters and theE. coli Na⁺/proline cotransporter (putP). The rabbit intestinal Na⁺/glucose cotransporter has 11 potential membrane spanning regions and 2 hydrophilic regions containing highly charged residues. The amino acid sequence shows two potential N-glycosylation sites (N-X-T/S). Using an in vitro translation approach we were able to determine that only one of these (Asn 248) is glycosylated. Expression experiments withXenopus oocytes using the N-glycosylation inhibitor tunicamycin indicate that glycosylation of Asn 248 is required for functional expression of the transporter. The N-X-T/S sequence at Asn 248 is conserved in the human intestinal and the human renal Na⁺/glucose cotransporter. Chromosomal localization studies map the human intestinal Na⁺/glucose cotransporter gene (SGLT1) to the q11.2qter region of chromosome 22 and the human renal Na⁺/glucose cotransporter gene (SGLT2) to the q-arm of chromosome 16. Thus the intestinal and renal Na⁺/glucose cotransporters are encoded by different genes located on different chromosomes. This is consistent with the observation that inherited defects of the transporters, intestinal glucose/galactose malabsorption and renal glycosuria, do not appear to be genetically linked.     

The influence of buffer pH,glucose and sodium ion concentration on the acid microclimate in rat proximal jejunum in vitro

Surface pH of rat proximal jejunum as measured in vitro by pH-electrode was found to be significantly more acid than bulk bathing media of neutral pH. Below a bulk pH value between pH 4 and 5, surface pH was isohydric with bulk pH but with increasing alkalinity of the bulk pH, surface pH remained consistently more acidic. The maintenance of a low surface pH was sensitive to external medium glucose concentration, particularly between 2 and 10 mM concentration. A Lineweaver-Burk plot of the glucose-dependent decrement in surface pH demonstrated an apparentK _m of 2 mM. Anoxia caused a significant elevation in the measured surface pH at 10 mM glucose concentration. Surface pH was found to be sensitive to buffer sodium ion concentration in the jejunum, an effect which was less marked in the distal ileum.The measured low pH at the mucosal surface of rat jejunum experimentally confirms the acid-microclimate hypothesis for drug absorption as originally proposed by Schanker and colleagues. The existence of a low pH has important consequences for the intestinal absorption of dissociable compounds. The implication for the experimental verification of active transport of solutes capable of dissociation is discussed.     

Histopathological phenotypes of early gastric cancer and its background mucosa

Recent advances in endoscopic submucosal dissection (ESD) techniques contribute to endoscopic treatment of early gastric cancer (EGC). Recognition of chronic atrophic gastritis as the background is important for high-quality detection and diagnosis of EGC. But, relationships between EGC and atrophy of the background gastric mucosa caused by Helicobacter pylori are not well understood. The present study demonstrated histopathological phenotypes of EGC, as well as chronic atrophic gastritis as background mucosa of EGC. We evaluated mucosal heights, number of glands, and degree of intestinal metaplasia (IM) of the background gastric mucosa, using 81 cases of EGC resected by ESD. Gastric phenotype cancer cases showed IM of the background gastric mucosa less frequently, compared with intestinal phenotype cancer cases (score of IM, 1.15 vs. 1.65, P = 0.012). The average mucosal heights around EGC were lower in moderately to poorly differentiated adenocarcinoma cases than well differentiated adenocarcinoma cases (442.6 μm vs. 500.2 μm, P = 0.011). The mucosal atrophy indicated by average heights of background mucosa was low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancercases (452.8 μm vs. 505.6 μm, P = 0.018). In the fundic gland area, the mucosal heights were low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancer cases (413.2 μm vs. 495.5 μm, P = 0.015). Our results using EGC specimens indicated that gastric phenotype cancer and moderately to poorly differentiated adenocarcinoma had atrophic background mucosa with lower mucosal heights and less IM. The atrophic gastric mucosa with less IM is thought to play an important role in gastric carcinogenesis, especially tumoriogenesis of gastricphenotype cancer.     

Effect of proquazone and indomethacin on gastric prostaglandin synthesisin vitro andin vivo

Although proquazone is less ulcerogenic than indomethacin in rat and man, it inhibits more effectively than indomethacin gastric mucosal synthesis of 6-keto-prostaglandin (PG) F₁ in both species during incubationin vitro. The more pronounced inhibitory activity of proquazone can be observed on formation of 6-keto-PGF₁ from endogenous substrate by fragments of gastric mucosa as well as on conversion of exogenous arachidonic acid by a microsomal fraction of mucosal homogenates indicating high affinity of proquazone for gastric mucosal cyclo-oxygenase. After oral administration, however, both drugs exhibit equal inhibitory potency on gastric formation of 6-keto-PGF₁ in the rat. These findings indicate that pharmacokinetic properties of non-steroidal anti-inflammatory drugs (NSAID) contribute significantly to their inhibitory action on gastric PG formationin vivo. The comparable reduction of gastric 6-keto-PGF₁ synthesis observed after oral administration of proquazone and indomethacin in the rat suggests that the ulcerogenic effects of NSAID result not only from inhibition of the gastric PG system. Effects on other processes and other enzyme systems, e.g. the lipoxygenase pathway of arachidonic acid metabolism, may modulate drug-induced ulcerogenicity and deserve further investigation.     

Expression of Trefoil Peptides in The Gastric Mucosa of Transgenic Mice Overexpressing Transforming Growth Factor-α

Abstract

Overexpression of transforming growth factor-α (TGF-α) in the gastric mucosa of metallothionein-TGFα(MT-TGFα) transgenic mice leads to a marked alteration in the ontogeny of the fundic cellular lineages. Induction of the transgene leads to the over-production of mucous cells with a concomitant diminution in the development of parietal cell and chief cell lineages. We have sought to define more precisely the mucous cell lineages involved in the mucous cell hyperplasia in MT-TGFα mice by investigating the expression of trefoil peptides in MT-TGFα mice. MT-TGFα mice and their non-transgenic littermates were treated with cadmium sulfate beginning at 13 days of age. Animals were then sacrificed at intervals over the following 2 weeks and gastric mucosa was examined for expression of trefoil peptides and TGFα by immunohistochemistry and in situ hybridization. No TGFα mRNA expression could be demonstrated by in situ hybridization in non-transgenic mice. In MT-TGFα mice, in situ grains for TGFα mRNA were detected at the base of fundic glands in 13 day old animals, whereas the expression was observed more widely in the mucosa of older animals (28 days). TGFα immunoreactivity was observed in foveolar mucous cells and residual parietal cells in MT-TGFα mice at all ages. By in situ hybridization, pS2 mRNA was detected in the surface mucous cells in normal gastric mucosa. In MT-TGFα mice, pS2 mRNA was found throughout the expanded foveolar region. By in situ hybridization, spasmolytic peptide (SP) expression was observed in the region of the progenitor zone in both groups of mice. By immunohistochemistry, SP expression was noted in a broad band of mucous neck cells deep to the progenitor zone. No gastric expression of intestinal trefoil factor (ITF) was noted in either group of mice. The results demonstrate that the expansion of the foveolar mucous cell compartment in MT-TGFα mice is due to the hyperplasia of normal surface cells expressing their particular mucin-associated trefoil peptide, pS2.     

The inactivation of extracellularly administered amino acids in the feline spinal cord

Summary The mercurials, p-hydroxymercuribenzoate and p-chloromercuriphenylsulphonate, administered electrophoretically from multi-barelled micropipettes, potentiate the depressant action of similarly administered glycine on feline spinal neurones. In addition, these mercurials inhibit the transport of glycine into rat brain slices. Neither action is very specific for glycine, since slightly higher concentrations of p-chloromercuriphenylsulphonate than those required to potentiate glycine-induced depression also potentiate depression induced by GABA, -alanine, Land D--alanine, and even higher concentrations enhance the excitant action of acidic amino acids. p-Hydroxymercuribenzoate also inhibits the uptake of GABA, DL-aspartate and L-lysine by brain slices. The potentiation by the mercurials of amino acid-induced effects is considered likely to be the result of inhibition of transport processes rather than enzymic activities.Thiosemicarbazide, administered electrophoretically and intravenously, does not enhance the effects of amino acid excitants or depressants on spinal interneurones. Hydrazinopropionic acid, a potent inhibitor of GABA transaminase, does not enhance GABA-induced depression of spinal interneurones when administered electrophoretically.These findings suggest the importance of transport processes in the removal of amino acids from the synaptic environment, and evidence is discussed that these processes are likely to differ in detail from the observed gross transport of amino acids into tissue slices.     

Gastric antral and fundic mucosal protein,DNA and RNA changes in different experimental ulcer models

The changes in gastric (fundic and antral) mucosal protein, DNA and RNA content, have been investigated in different experimental gastric ulcer models of rat. It seems that indomethacin and stress (restraint) ulcer formation were followed by a predominant fundic (oxyntic cell area) mucosal DNA increase, while in the antral mucosa this phenomenon was connected to a significant RNA increase.The observed changes of the RNA/DNA ratio in the fundic mucosa were interpreted as a sign of accelerated cell renewal. The authors conclude that during ulceration the regenerative processes concomitantly take place.     

Phosphopyridoxal cyclic compounds with histamine and histidine. 6: The formation of phosphopyridoxal cyclic compounds with histamine and histidine in the presence of biological material

We have studied the dynamics of cyclic compound formation between histamine or histidine and pyridoxal 5-phosphate (Hi-PLP or His-PLP) in incubates of rat gastric mucosa histidine decarboxylase (HD), rat intestinal diamine oxidase (DAO) or homogenates of either rat liver, intestine or gastric mucosa. For gastric mucosa HD, liver and gastric mucosa homogenates, the rate of cyclization was slightly decreased; however, the rate was significantly inhibited with intestinal DAO or intestinal homogenate. Binding of PLP by tissue components was measured; free PLP was bound abundantly by rat intestinal DAO and by rat intestinal homogenate.A possible mechanism by which intestinal tissues inhibit cyclic compound formation is discussed.     

Repair of gastric ulcer

Summary By a cryosurgical method a mucosal defect was produced in the body of the rat stomach, and repair of the gastric ulcer was studied with ³H-thymidine autoradiography. From 18 to 24 hours after cryoinjury, cell proliferation in the fundic mucosa was much increased, as indicated by an increase in the labeling index of the cells in the proliferating cell zone of the mucosa, or by reactive incorporation of ³H-thymidine into the mucous neck, chief and parietal cells. Spatially, the increased cell proliferation was found in a region of the mucosa more than 600 rn distant from the injury, and lasted for more than 14 days. The mucous neck and chief cells around the ulcer which had incorporated ³H-thymidine seemed to transform into flat cells after mitotic division and then continued to divide. After 3–5 days, so called regenerating epithelium or covering epithelium appeared around the ulcer. The upper part of this regenerating epithelium consists of tall columnar cells, the lower part is composed of cystic glandular structures, in which many ³H-thymidine incorporating cells were seen. The formation of new glands in the mucosal defect appeared to take place by budding from these cystic glandular structures with subsequent differentiation of surface epithelial cells. After 3 weeks the mucosal defect was covered by mucinous glandular structures similar to the proper pyloric mucosa. The proliferating cells were confined to the middle level in the regenerated mucosa.Dedicated to Professor Dr. W. Maurer on the occasion of his 75^th birthdayThis work was supported by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, He 537/5Scholar of the Alexander von Humboldt-Foundation     

Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in Mongolian gerbils

Although regenerating gene (Reg) protein is reported to have a trophic effect on gastric epithelial cells, its involvement in human gastric diseases is not clear. We have recently shown that both gastrin and gastric mucosal inflammation enhance Reg gene expression in the fundic mucosa in rats. This study was designed to clarify whether Reg protein is involved in Helicobacter pylori-induced gastritis and whether Reg gene expression is linked to serum gastrin levels in this condition. Mongolian gerbils were inoculated with an H. pylori strain isolated from a gastric cancer patient. Four weeks later, some of the gerbils with H. pylori infection were eradicated by lansoprazole, amoxicillin, and clarithromycin. The time courses of changes in Reg gene expression, serum gastrin levels, gastric acidity, and histopathologic factors were examined. Four weeks after H. pylori infection, gastritis started spreading to the fundic mucosa, and gastric acidity started reducing. Serum gastrin levels and Reg mRNA expression in the fundus were significantly increased 6 weeks after infection. Reg mRNA expression in the fundus correlated significantly with both serum gastrin levels and the severity of fundic mucosal inflammation. After H. pylori eradication, serum gastrin levels and fundic mucosal inflammation were normalized, and the increase in Reg mRNA expression was abolished. The Reg gene is associated with hypergastrinemia and fundic mucosal inflammation and may be involved in H. pylori-induced gastritis.     

Changes of endogenous prostacyclin-level in different experimental gastroduodenal ulcer models of rat

It seems that the gastric antral mucosa either in normal, physiological circumstances, or in IND or STR induced gastric ulcer models, contains significantly more endogenous PG-I₂ than that of gastric fundic, mucosa, while the duodenal mucosa contains significantly lower endogenous PG-I₂-level compared to the gastric antral or fundic level.Either in gastric or in duodenal ulceration, the endogenous PG-I₂ level basically decreased proportionally to the degree of ulceration—therefore it is tempting to speculate that the endogenous PG-I₂ is most probably one of thenatural protective substances in the gastrointestinal mucosa.     

Acute gastric lesions induced by the administration of histamine to rats with partial vascular occlusion: evidence for the gastroprotective effect of prostaglandin

Introduction

Histamine is not only a potent stimulator of gastric acid secretion, but it also plays a central role in gastroduodenal ulcerogenesis. In the present study we tested the effect of pre-treatment with exogenous prostaglandin E₂ (PGE₂) in a new rat model of experimental gastric ulcers induced by combination of histamine and gastric ischemia.

Methods

In male Wistar rats, a chronic ischemia of gastric mucosa was induced via the clamping of the left gastric artery and vein (L-AV) in combination with pylorus ligation. The following treatment groups of rats (6 rats/group) were investigated: 1) histamine alone (40 mg/kg twice s.c.); 2) vehicle (saline) followed 30 min later by gastric mucosal L-AV ischemia and pylorus ligation combined with histamine (40 mg/kg twice s.c.) and 3) PGE₂ (5 µg/kg i.g.) followed 30 min later by gastric mucosal L-AV ischemia combined with histamine (40 mg/kg twice s.c.) and pylorus ligation. At 4 hr after the clamping of L-AV and pylorus ligation, the area of gastric lesions and gastric acid secretion was determined.

Results

Histamine treatment failed to produce gastric lesions, but when it was combined with ischemia, the widespread gastric lesions in the corpus mucosa, but not in the antrum, were observed. This damaging effect and decrease in the GBF were significantly attenuated by pretreatment with PGE₂.

Conclusion

The present study demonstrates that gastric hypersecretion induced by histamine in combination with gastric mucosal ischemia results in gastric lesions which progress into chronic gastric ulcers.

     

Effect of 13-NLE-motilin on gastric secretion, serum gastrin level and mucosal blood flow in dogs.

1. In dogs with gastric fistulas and vagally innervated fundic and antral pouches, 13-norleucine-motilin (13-nle-motilin), a synthetic analogue of motilin, infused intravenously in graded doses produced a dose-dependent increase in gastric acid and pepsin outputs. 2. The motilin-induced stimulation of gastric secretion occurred independently of antral pH and was not accompanied by any alteration in the serum gastrin level suggesting that motilin did not affect the release of gastrin. 3. When infused intravenously in a constant dose against a constant background stimulation with pentagastrin or histamine 13-nle-motilin inhibited both acid and pepsin secretion from the main stomach and fundic pouch. 4. The inhibitory effect of 13-nle-motilin was always associated with a marked reduction in mucosal blood flow but without any change in the ratio of aminopyrine concentration in the gastric juice and blood plasma indicating that this peptide primarily affected gastric secretion but did not limit the gastric mucosal microcirculation.