Interstitital cells of Cajal in the human stomach: distribution and relationship with enteric innervation

Interstitial cells of Cajal (ICC) are distributed throughout the gastrointestinal muscle coat with a region-specific location, and are considered to be pace-maker and/or mediators of neurotransmission. Little is known about their shape, size, distribution and relationships with excitatory and inhibitory nerves in human stomach. With this aim, we labeled the ICC, using c-Kit immunohistochemistry, followed by a quantitative analysis to evaluate the distribution and area occupied by these cells in the circular and longitudinal muscle layers and at the myenteric plexus level in the human fundus, corpus and antrum. Furthermore, by NADPH-d histochemistry and substance P (SP) immunohistochemistry, we labeled and quantified nitric oxide (NO)-producing and SP-containing nerves and evidenced their relationships with the ICC in these three gastric regions. In the fundus, the ICC appeared as bipolar cells and in the corpus and antrum they mainly appeared as multipolar cells, with highly ramified processes. The networks formed by ICC differed in the three gastric regions. The ICC number was significantly higher and cell area smaller in the fundus compared to the corpus and antrum. The area occupied by the ICC was significantly higher at the myenteric plexus level compared with circular and longitudinal muscle layers. Everywhere, NADPH-d-positive nerves were more numerous than SP-positive ones. Both kinds of fibers were closely apposed to the ICC in the corpus and antrum. In conclusion, in the human stomach, the ICC have region-specific shape, size and distribution and in the corpus and antrum have close contact with both inhibitory and excitatory nerves. Presumably, as suggested for laboratory mammals, these differences are in relationship with the motor activities peculiar to each gastric area.     

Distribution of bombesin-like peptides in the alimentary canal of several vertebrate species

The objective of this study was to quantitate and characterize the variants of bombesin-like immunoreactivity in the alimentary canal of the rat, rabbit, hawk, owl, dog, monkey and human. Bombesin-like immunoreactivity was found throughout the entire gastrointestinal tract of all species studied. In the rat, the highest concentration of bombesin-like immunoreactivity was found in the colon. Gel chromatography showed that bombesin-like immunoreactivity corresponded to gastrin-releasing peptide (GRP-27) and GRP-10. In the dog, the greatest concentration of bombesin-like immunoreactivity was observed in the mucosal layer of the fundus, whereas the concentration of bombesin-like immunoreactivity in the muscle layer of the dog did not vary significantly from region to region. Gel chromatography showed that bombesin-like immunoreactivity in the dog corresponded to GRP-27, bombesin, GRP-10, and a smaller fragment. In the human, the concentration of bombesin-like immunoreactivity did not vary significantly from region to region in the mucosal and muscular layers. Gel chromatography of human fundal mucosa showed that bombesin-like immunoreactivity peaks occur in the regions of GRP-27, bombesin and GRP-10. These findings substantiate the observation that bombesin-like peptides play a variety of roles in the regulation of gut function.     

Identification and regional distribution of the dopamine D(1A) receptor in the gastrointestinal tract

Dopamine (DA) is regarded as an important modulator of enteric function. Recent experiments have suggested that newly cloned DA receptor subtypes are widely expressed in peripheral organs, including the gastrointestinal tract. In the present studies, the D(1A) receptor subtype was identified in rat gut regions through localization of receptor protein by means of light microscopic immunohistochemistry and Western blot analysis and receptor mRNA by RT-PCR and in situ amplification and hybridization (3SR in situ). D(1A) receptor immunoreactivity was shown to have a diverse distribution in the gastrointestinal tract, being present in the gastroesophageal junction, stomach, pylorus, small intestine, and colon. The receptor has a transmural distribution present in both epithelial and muscle layers as well as in blood vessels and lamina propria cells of different gastrointestinal regions. Western blot analysis demonstrated a single 50-kDa band for esophagus, stomach, duodenum, jejunum, and colon. The in situ hybridization signal was localized to the same sites revealed by D(1A) receptor immunoreactivity. RT-PCR revealed an appropriate sized signal in similar regions. This study is the first to identify expression of the central D(1A) receptor throughout the normal mammalian gastrointestinal tract.     

Expression of intermediate conductance potassium channel immunoreactivity in neurons and epithelial cells of the rat gastrointestinal tract

Recent functional evidence suggests that intermediate conductance calcium-activated potassium channels (IK channels) occur in neurons in the small intestine and in mucosal epithelial cells in the colon. This study was undertaken to investigate whether IK channel immunoreactivity occurs at these and at other sites in the gastrointestinal tract of the rat. IK channel immunoreactivity was found in nerve cell bodies throughout the gastrointestinal tract, from the esophagus to the rectum. It was revealed in the initial segments of the axons, but not in axon terminals. The majority of immunoreactive neurons had Dogiel type II morphology and in the myenteric plexus of the ileum all immunoreactive neurons were of this shape. Intrinsic primary afferent neurons in the rat small intestine are Dogiel type II neurons that are immunoreactive for calretinin, and it was found that almost all the IK channel immunoreactive neurons were also calretinin immunoreactive. IK channel immunoreactivity also occurred in calretinin-immunoreactive, Dogiel type II neurons in the caecum. Epithelial cells of the mucosal lining were immunoreactive in the esophagus, stomach, small and large intestines. In the intestines, the immunoreactivity occurred in transporting enterocytes, but not in mucous cells. Immunoreactivity was at both the apical and basolateral surfaces. A small proportion of mucosal endocrine cells was immunoreactive in the duodenum, ileum and caecum, but not in the stomach, proximal colon, distal colon or rectum. There was immunoreactivity of vascular endothelial cells. It is concluded that IK channels are located on cell bodies and proximal parts of axons of intrinsic primary afferent neurons, where, from functional studies, they would be predicted to lower neuronal excitability when opened in response to calcium entry. In the mucosa of the small and large intestine, IK channels are probably involved in control of potassium exchange, and in the esophageal and gastric mucosa they are possibly involved in control of cell volume in response to osmotic challenge.     

E2 and not P4 increases NO release from NANC nerves of the gastrointestinal tract: implications in pregnancy

In women, during pregnancy, there is decreased motility of the gastrointestinal tract leading to a delay in gastric emptying and an increase in colonic transit time. Whether the rise in estradiol (E2) or progesterone (P4) is responsible for this effect is controversial. As the nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves is responsible for modulating gastrointestinal motility in vivo, the purpose of this study was to evaluate whether the increased release of nitric oxide (NO) from the nitrergic component of the NANC nerves innervating the gastric fundus and colon that occurs during late pregnancy in rats is mediated by E2 or P4. Ovariectomized rats treated with E2 or P4 alone or in combination were used for our studies. We also wanted to assess the cellular and molecular mechanisms involved. The NANC activity was studied by assessing changes in tone after application of electric field stimulation (EFS). The role of NO was determined by observing the effects of EFS in the presence and absence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the reversibility of the effects of L-NAME by L-arginine. Our studies indicated that there was increased magnitude of relaxation of isolated strips of rat gastric fundus and rat colon after application of EFS to tissues obtained from animals treated with E2 alone or a combination of E2 + P4 but not from those treated with P4 alone. L-NAME attenuated relaxation responses in E2- and E2 + P4-treated animals. To elucidate whether the increased NO release may be due to an increase in neuronal NOS (nNOS) protein, we used both Western blot analysis and immunohistochemistry. We also used RT-PCR to determine whether there was an increase in nNOS mRNA after treatment with sex steroids. In nonpregnant animals, nNOS was detected by Western blot in the fundus and the colon and was barely detectable in the ileum. In pregnancy, there was an increase in nNOS in both the gastric fundus and the colon. The nNOS protein was also increased in ovariectomized animals treated with either E2 alone or E2 + P4 but not P4 alone when compared with ovariectomized animals receiving vehicle. Our results indicated that there was an increase in nNOS protein that was localized to the neurons of the myenteric plexus in the gastric fundus and colon in E2- and E2 + P4-treated animals, but this increase was not observed in animals treated with P4 alone. This increase in nNOS protein was accompanied by an increase in nNOS mRNA. These results suggest the possibility that E2, rather than P4, may be responsible for the delay in gastric emptying and increase in colonic transit time observed in pregnancy.     

Immunolocalization of histamine H3 receptors on endocrine cells in the rat gastrointestinal tract

The histamine H3 receptor (H3R) has been identified in the gastrointestinal tract of the rat by immunohistochemistry, using the first validated anti-H3 receptor antibody. Immunoreactivity to H3R was exclusively localized to the endocrine cells scattered in the gastrointestinal mucosa, with positive cells being prominently abundant in the gastric fundus, while they were rarely found in the other regions. In the fundus, positive cells were distributed in the lower half of the mucosa and their number significantly decreased after a 24 h-fasting period. Double-labeling studies were undertaken to identify the H3R-immunoreactive cell types in the fundic and antral mucosa. The H3R-immunoreactive cells were positive for chromogranin A. In the fundus, approximately 90% of cells positive to H3R were also positive to the histamine-forming enzyme, histidine decarboxylase. None of the cells expressing H3R displayed immunoreactivity for gastrin, somatostatin or ghrelin. Location, the influence of food deprivation and colocalization with histidine decarboxylase indicate that H3R positive cells correspond to the enterochromaffin-like cells (ECL).     

Effect of cisapride on the concentrations of beta-endorphinlike immunoreactivity and substance P-like immunoreactivity in the rat gastrointestinal tract

Cisapride is a gastrointestinal prokinetic agent reported to be devoid of direct cholinergic effect from the myenteric plexus of the gut. The effect of cisapride (0.125, 0.5, 2mg/kg, i.p.) on the concentration beta-endorphin and substance P in rat gastrointestinal tract was studied. beta-Endorphinlike immunoreactivity contents were significantly increased in both mucosal and muscular layers of the entire gastrointestinal tract (from gastric body to rectum) of the rats treated with 2 mg/kg of cisapride. beta-Endorphinlike immunoreactivity contents were also increased in a part of the gastrointestinal tract of the rats treated with 0.125 or 0.5 mg/kg of cisapride. Substance P like immunoreactivity contents were significantly decreased in muscular layers of the rectosigmoid colon of the rats treated with 2 mg/kg of cisapride. This study suggests that the prokinetic effects of cisapride may relate to the contents of beta-endorphinlike immunoreactivity and substance P like immunoreactivity in gastrointestinal tract.     

hERG1 Potassium Channel Expression in Colorectal Adenomas: Comparison with Other Preneoplastic Lesions of the Gastrointestinal Tract

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett’s esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett’s esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract.     

Diabetes mellitus is associated with a decrease in vasoactive intestinal polypeptide content of gastrointestinal tract of rat

Vasoactive intestinal polypeptide (VIP) is an inhibitory non-adrenergic, non-cholinergic transmitter, which mediate in the relaxation of sphincters of the gastrointestinal tract. The aim of this study was to determine whether there is a change in the pattern of innervation and tissue content of VIP in the rat gastroduodenum after the onset of streptozotocin (STZ)-induced diabetes mellitus. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg Kg(-1)). Four weeks after the induction of diabetes mellitus, the rats were anaethetised and the pancreata were removed for further processing. VIP was localized and measured in normal and diabetic rat gastroduodenal tissues by immunohistochemistry and radioimmunoassay, respectively. VIP immunoreactivity was stronger in the ganglion cells of the submucosal and myenteric plexuses of the gastric antrum and duodenum of normal rats (n = 6) when compared to that of diabetic rats (n = 6). Moreover, the number of VIP-positive neurons was significantly lower in the gastrointestinal tract of diabetic rats compared to normal. The VIP content of the gastric antrum and duodenum of diabetic rat was significantly lower (p< 0.05) than that of normal rat. In contrast to the lower tissue levels of VIP in the gastroduodenal segment of diabetic rats, the plasma level of VIP was significantly higher (p< 0.04) in diabetic rat compared to normal. The plasma level of VIP in normal rats was comparable to that measured in normal human beings. A low tissue level of VIP in the gastroduodenal tract of diabetic rat may contribute in part to the abnormal gut motility observed in diabetic patients.     

Expression of the ammonia transporter proteins Rh B glycoprotein and Rh C glycoprotein in the intestinal tract

Ammonia metabolism is important in multiple aspects of gastrointestinal physiology, but the mechanisms of ammonia transport in the gastrointestinal tract remain incompletely defined. The present study examines expression of the ammonia transporter family members Rh B glycoprotein (RhBG) and Rh C glycoprotein (RhCG) in the mouse gastrointestinal tract. Real-time RT-PCR amplification and immunoblot analysis identified mRNA and protein for both RhBG and RhCG were expressed in stomach, duodenum, jejunum, ileum, and colon. Immunohistochemistry showed organ and cell-specific expression of both RhBG and RhCG. In the stomach, both RhBG and RhCG were expressed in the fundus and forestomach, but not in the antrum. In the forestomach, RhBG was expressed by all nucleated squamous epithelial cells, whereas RhCG was expressed only in the stratum germinativum. In the fundus, RhBG and RhCG immunoreactivity was present in zymogenic cells but not in parietal or mucous cells. Furthermore, zymogenic cell RhBG and RhCG expression was polarized, with apical RhCG and basolateral RhBG immunoreactivity. In the duodenum, jejunum, ileum, and colon, RhBG and RhCG immunoreactivity was present in villous, but not in mucous or crypt cells. Similar to the fundic zymogenic cell, RhBG and RhCG expression in villous epithelial cells was polarized when apical RhCG and basolateral RhBG immunoreactivity was present. Thus the ammonia transporting proteins RhBG and RhCG exhibit cell-specific, axially heterogeneous, and polarized expression in the intestinal tract suggesting they function cooperatively to mediate gastrointestinal tract ammonia transport.     

Distribution of prostaglandin E receptors in the rat gastrointestinal tract

: In order to study the role of prostaglandin in the regulation of the gastrointestinal functions, gene expression of prostaglandin receptors along the rat gastrointestinal tracts were investigated.

: Rats were used for the study. The combination of counterflow elutriation separation of mucosal cells and Northern blot analysis was used to detect the gene expression of prostaglandin receptors in gastrointestinal tracts.

: In small intestine and colon, prostaglandin E2 EP1 and EP3 receptor mRNAs were mainly localized in the deeper intestinal wall containing muscle layers. EP4 receptor gene expression, on the other hand, was detected in the intestinal mucosal layer.

In the stomach, EP1 mRNA was detected in gastric muscle layers, whereas EP3 and EN receptor gene expression was mainly present in the gastric mucosal layer containing epithelial cells. In gastric epithelial cells, parietal cells were found to have both EP3 and EP4 receptors. At lower concentrations, prostaglandin E2 inhibited gastric acid secretion by parietal cells probably through EP4 receptors. At higher concentrations, however, it stimulated it. On the other hand, mucous cells possessed only EP4 receptor mRNA.

: Thus, it is suggested that prostaglandin E2 modulates gastrointestinal functions through at least three different prostaglandin receptors (EP1, EP3, and EP4), each of which has a distinct distribution in the gastrointestinal tract.     

Involvement of ghrelin-growth hormone secretagogue receptor system in pathoclinical profiles of digestive system cancer

Ghrelin receptor has been shown to be expressed along the human gastrointestinal tract. Recent studies showed that ghrelin and a synthetic ghrelin receptor agonist improved weight gain and lean body mass retention in a rat model of cancer cachexia by acting on ghrelin receptor, that is, growth hormone secretagogue receptor （GHS-R）. This study aims to explore the expression and the distribution of ghrelin receptor in human gastrointestinal tract cancers and to investigate the possible involvement of the ghrelin- GHS-R system in human digestive cancers. Surgical human digestive cancer specimens were obtained from various portions of the gastrointestinal tract from different patients. The expression of ghrelin receptor in these tissues was detected by tissue microarray technique. Our results showed that ghrelin receptor was expressed in cancers throughout the gastrointestinal tract, mainly in the cytoplasm of mucosal layer cells. Its expression level possibly correlated with organ type, histological grade, tumor-nodes-metastases stage, and nutrition status （weight loss） of the patients. For the first time, we identified the distribution of ghrelin receptor in digestive system cancers. Our results implied that the ghrelin-GHS-R system might be involved in the pathoclinical profiles of digestive cancers.     

Immunocytochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the rat stomach

Summary Prostaglandins are considered to play important roles in gastric mucosal protection. The rate-limiting enzyme involved in the biosynthesis of prostaglandins is cyclooxygenase (COX), also known as prostaglandin H synthase. Two forms of COX are known: a constitutively expressed form (COX-1) and a newly-characterized, inducible form (COX-2). In the present study, the immunocytochemical localization of COX-1 and COX-2 was examined in the rat gastrointestinal tract. A strong immunoreactivity for COX-1 was localized in the mucous neck cells of gastric gland. A weak reactivity for COX-1 was also found in the mucous cell types in the cardiac gland and pyloric gland of the stomach as well as in the Brunner's gland of duodenum. Ultrastructurally, the immunoreactivity was localized to the apical cytoplasm of these cells. On the other hand, immunoreactivity for COX-2 was distributed in the surface mucous cells in both the fundic and pyloric regions of stomach. These results suggest that a subset of mucous cells is the primary site for production of prostaglandins in the rat gastrointestinal tract, and that two forms of COX are expressed in distinct types of mucous cell.     

Neuronal nitric oxide synthase: expression in rat parietal cells

Nitric oxide synthases (NOS) are enzymes that catalyze the generation of nitric oxide (NO) from L-arginine and require nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. At least three isoforms of NOS have been identified: neuronal NOS (nNOS or NOS I), inducible NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS II). Recent studies implicate NO in the regulation of gastric acid secretion. The aim of the present study was to localize the cellular distribution and characterize the isoform of NOS present in oxyntic mucosa. Oxyntic mucosal segments from rat stomach were stained by the NADPH-diaphorase reaction and with isoform-specific NOS antibodies. The expression of NOS in isolated, highly enriched (>98%) rat parietal cells was examined by immunohistochemistry, Western blot analysis, and RT-PCR. In oxyntic mucosa, histochemical staining revealed NADPH-diaphorase and nNOS immunoreactivity in cells in the midportion of the glands, which were identified as parietal cells in hematoxylin and eosin-stained step sections. In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR. Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity). Expression of nNOS in parietal cells suggests that endogenous NO, acting as an intracellular signaling molecule, may participate in the regulation of gastric acid secretion.     

Immunohistochemical distribution of hepatic fatty acid-binding protein in rat and human alimentary tract

Tissues from rat and human alimentary tract were immunostained with rabbit antibodies to fatty acid-binding protein (FABP) isolated from rat liver, since the precise immunohistochemical localization of the protein in gut has not been determined. The results obtained indicated that FABP immunoreactivity was found almost exclusively in intestinal absorptive cells, the sole exception being its presence in the cytoplasm of a few goblet cells. In small bowel, FABP-positive cells were most often found in the upper and middle segments, and less frequently in the lower to terminal portion. Immunoreactive cells were also found in large bowel of rat and human, but with differing patterns of distribution. In rat, positive cells were found mainly in the lower portion of the large intestine, whereas in human positive cells were present in all portions. Immunoreactive cells were detected in rat and human cecum, in the upper half of human rectum, and in human vermiform appendix. No such cells were found in esophageal and nonmetaplastic gastric mucosa or in pancreatic tissue, whereas they were present in great numbers in metaplastic gastric mucosa. The results of this study therefore suggest that FABP is a useful marker for research into the physiology or pathology of absorptive cells in the gastrointestinal tracts of both species.     

Arginine-vasopressin immunoreactive material in the gastrointestinal tract

Like many other neuropeptides, vasopressin is not confined to the hypothalamic neurohypophysial system. Furthermore, vasopressin was found to be a potent vasoconstrictor in the rat jejunum, reducing myenteric artery flow. These associations were the basis of this investigation on the presence of vasopressin in the gastrointestinal (GI) tract by both RIA and immunohistochemistry. Portions of the gastrointestinal tract and pancreatic islets of the rat were extracted with 0.1 N HCl for RIA measurements of AVP content. Similar portions from the male cat GI tract were used for immunohistochemistry studies. Acid extracts of the GI tract were found to contain immunoreactive AVP with the highest concentration (pg/mg protein) in the fundus portion of the stomach (15.0 +/- 1.6) and slightly lower values down along the antrum-pylorus portion (6.7 +/- 0.6), proximal jejunum (8.6 +/- 0.2), distal ileum (9.7 +/- 0.3) and colon (11.9 +/- 0.5). In the pancreatic islets the concentration was much higher (72.0 pg/mg protein). The extract inhibition curves showed parallelism with the appropriate standard preparation of AVP in the specific RIA. Immunohistochemical localization showed IR-AVP in the nerve fibers around the myenteric plexus of the second portion of the duodenum. It was also found in fibers starting from where the myenteric plexus goes through the layer of muscle fibers, penetrating the submucosa and duodenal mucosa, ending near the capillaries situated along the basal side of the villous epithelium cells. Similar IR-AVP activity was found in cells located in the mucosal epithelium of the duodenum, jejunum, ileum, colon and rectum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bombesin-like immunoreactivity in human gastrointestinal tract

In the present study the distribution and molecular characteristics of bombesin-like immunoreactivity (BLI) were studied in acid extracts of human gastrointestinal tract. The highest levels were found in the fundus, antrum, pylorus and pancreas with lower levels in the duodenum, jejunum, terminal ileum and colon. BLI was also detected in both the muscle and mucosal layers of the antrum and colon. Sephadex G-50 gel chromatography under acid dissociating conditions revealed two peaks of immunoreactivity, one in the position of synthetic porcine gastrin releasing peptide (GRP) and the second eluting with synthetic amphibian bombesin. Variations in the proportions of the two molecular forms were seen in different regions of the gut. In the stomach and pancreas greater than 70% of the BLI eluted with the GRP marker while in pylorus, jejunum and terminal ileum only 20% was present in this form. Reverse-phase ODS silica HPLC of the major antral BLI peak, utilising a methanol/trifluoroacetic acid gradient indicated that this peptide was similar to porcine GRP. We have therefore (1) demonstrated the presence and heterogeneity of bombesin-like immunoreactivity throughout the human gastrointestinal tract and (2) shown for the first time that a proportion of this BLI closely resembles porcine GRP.     

Arginine-vasopressin immunoreactive material in the gastrointestinal tract

Summary Like many other neuropeptides, vasopressin is not confined to the hypothalamic neurohypophysial system. Furthermore, vasopressin was found to be a potent vasoconstrictor in the rat jejunum, reducing myenteric artery flow. These associations were the basis of this investigation on the presence of vasopressin in the gastrointestinal (GI) tract by both RIA and immunohistochemistry.Portions of the gastrointestinal tract and pancreatic islets of the rat were extracted with 0.1N HCl for RIA measurements of AVP content. Similar portions from the male cat GI tract were used for immunohistochemistry studies.Acid extracts of the GI tract were found to contain immunoreactive AVP with the highest concentration (pg/mg protein) in the fundus portion of the stomach (15.0±1.6) and slightly lower values down along the antrum-pylorus portion (6.7±0.6), proximal jejunum (8.6±0.2), distal ileum (9.7±0.3) and colon (11.9±0.5). In the pancreatic islets the concentration was much higher (72.0 pg/mg protein). The extract inhibition curves showed parallelism with the appropriate standard preparation of AVP in the specific RIA.Immunohistochemical localization showed IR-AVP in the nerve fibers around the myenteric plexus of the second portion of the duodenum. It was also found in fibers starting from where the myenteric plexus goes through the layer of muscle fibers, penetrating the submucosa and duodenal mucosa, ending near the capillaries situated along the basal side of the villous epithelium cells. Similar IR-AVP activity was found in cells located in the mucosal epithelium of the duodenum, jejunum, ileum, colon and rectum.These results show that the gastrointestinal tract of different species and pancreatic islets of the rat are a rich source of immunoreactive neurohypophysial AVP. Because of its distribution, this peptide might have some physiological significance in intestinal circulatory regulation.     

Transmucosal potential-difference profile in rat upper gastrointestinal tract. A simple model for testing gastric effects of pharmacologic agents

Transmucosal potential difference in the rat upper gastrointestinal tract is described by a simple in vivo technique. Values for potential difference between blood (reference) and lumen (in millivolts) were the following: esophagus, -13.7 +/- 1.6 (mean +/- SE); forestomach (rumen), -39.2 +/- 0.8; stomach fundus, -39.1 +/- 0.4; pylorus -26.6 +/- 0.6; and duodenum, -9.2 +/- 0.4. These values (excluding rumen) are strikingly similar to those obtained in man. Aspirin, taurocholic acid, and alcohol all produced falls in gastric potential difference very similar to those found in man. The rat appears to be a promising and convenient model for screening gastric effects of certain pharmacological agents before use in man.