Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Participation of capsaicin-sensitive afferent nerves in the gastric mucosa of patients with Helicobacter pylori-positive or-negative chronic gastritis.

Capsaicin-sensitive afferent nerves (CSANs) are involved in the protection of gastric mucosa. To clarify the role of CSANs in human Helicobacter pylori-negative or -positive chronic gastritis, after bacterium detection by rapid urease test, (14)C urea breath test, and specific histological staining, the immunodistribution of capsaicin receptor, calcitonin gene-related peptide (CGRP), and substance P (SP) was studied in 21 H. pylori-positive and 30 H. pylori-negative patients with chronic gastritis and 20 patients with functional dyspepsia (as histologically healthy controls). The expression of capsaicin receptor, CGRP, and SP was significantly higher in the mucosa of patients with chronic gastritis than in controls, however, no significant difference was obtained in the immunodistribution in patients with H. pylori-negative versus H. pylori-positive gastritis. In conclusion, CSANs participate in the development of human gastritis, however, their participation does not depend on the presence of Helicobacter pylori as a causative factor.

Co-infections with hepatitis G and TT virus in patients with chronic hepatitis C in Hungary.

The significance of co-infections with novel hepatitis viruses Hepatitis G (GBV-C, HGV) and TT virus (TTV) in chronic hepatitis C is not clear. We determined the prevalence of HGV RNA and TTV DNA in chronic hepatitis C patients and in asymptomatic hepatitis C virus (HCV) carriers, and assessed the influence of these agents on the course of HCV infection. Seventy-seven patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. Previous HBV infection was detected by testing serum HBsAg and aHBc. HGV RNA and TTV DNA were detected by PCR. In the healthy population, the prevalence of anti-HCV was 0.3%, HGV RNA 8.0% and TTV DNA 18.5%. In chronic hepatitis C HGV RNA occurred in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of HGV RNA was 9.09% and TTV DNA 75.7%. Neither HGV RNA nor TTV DNA had apparent effect on the HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.

Expanded parietal cell pool in transgenic mice unable to synthesize histamine.

BACKGROUND: The histidine decarboxylase enzyme (HDC) is responsible for the synthesis of histamine in mammals. Histidine decarboxylase-deficient (HDC-/-) mice have recently been developed by targeted mutation of the HDC gene. METHODS: The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a wash-through method for basal gastric acid secretion and by pylorus ligation for stimulated gastric acid secretion) and gastrin levels (by radioimmunoassay) in homozygous HDC-/- mice kept on a low-histamine diet. RESULTS: A double maximal gastric acid secretory response was found in knockouts after exogenous histamine administration. In contrast, the gastric acid secretion was significantly reduced after gastrinergic and cholinergic stimulation in the absence of histamine. The oxynthic gland area of HDC-/- mice was thickened with an increased parietal cell count compared to wild types. Substantially elevated serum and antral tissue gastrin levels of HDC-/- mice could be possible indications of both an expanded parietal cell mass and/or an increased histamine-induced maximal gastric acid secretory capacity of this genotype. CONCLUSIONS: These data suggest that not enough compensatory mechanisms develop in HDC-/- mice during a prolonged low-histamine diet to maintain/restore normal gastric acid secretion. An expanded parietal cell pool was also demonstrated in HDC-/- mice kept on a low-histamine diet, probably caused by a trophic effect of sustained hypergastrinaemia. The HDC-/- strain is a suitable model for studying the effects of achlorhydria and consequent hypergastrinaemia as an approach to human conditions such as atrophic gastritis or long-term antisecretory therapies.

Susceptibility of dopamine D5 receptor targeted mice to cysteamine.

BACKGROUND: Recently we demonstrated that gastric mucosa of rats can synthesize, store and release dopamine. Out of five different subtypes, mRNA of D5 (=D1b) dopamine receptor is very abundant in the gastric epithelium. D1 receptor selective dopamine agonists have been shown to protect against experimental gastro-duodenal lesions. AIMS: To test the hypothesis that protective effects of dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric acid secretion of D5 KO mice were also studied. METHODS: Single doses of 600 mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted animals. After 24 h, number and severity of gastro-duodenal lesions were analyzed. Basal and histamine-induced maximal gastric acid output were measured by a stomach-sac wash-through method. RESULTS: All the KOs in the 600 mg/kg cysteamine group died within 4 h showing symptoms of toxicity while three out of four WTs survived (P<0.05). Mortality after 300 mg/kg cysteamine was significantly higher in KOs versus the WTs: 6/14 versus 2/11, P<0.05. Gastric lesion-index was also significantly higher in KOs (median, middle quartile): four (3-9) versus 0 (0-0), P<0.05. Duodenal lesions did not develop from this single dose of cysteamine in either genotype. Basal and histamine-induced maximal gastric acid output were comparable in the two genotypes. CONCLUSIONS: This study demonstrates that loss of D5 receptor causes mucosal vulnerability and increased toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype is indeed likely to be involved in protective effects of dopamine in the stomach.

One year follow-up of patients after successful helicobacter pylori eradication therapy.

UNLABELLED: The aim of this study was to investigate the Helicobacter pylori (Hp) status of patients who underwent successful eradication therapy 1 year prior to the study and to evaluate their current symptoms. METHODS: all of the patients were initially evaluated by oesophago-gastro-bulboscopy and the Hp status was determined by at least two different methods [rapid urease test, histology or urea breath test (UBT)]. The Hp infection was treated with a 1-week triple therapy protocol, and the UBT was repeated 4-6 weeks later. We invited back 110 patients who had negative post-eradication UBT results 12+/-3 months prior to the study period. UBT was repeated and a questionnaire was completed about the previous and present complaints and medication. RESULTS: 80 of the 110 patients (73%) came back for the follow-up. Twenty five patients had peptic ulcer disease, 36 patients had gastritis or duodenitis without erosive lesions, and 19 patients had erosive form of gastritis or duodenitis initially. All of the patients except one in the erosive gastritis group had negative control UBT 1 year after the eradication, which means 1.25% recurrence rate within 1 year. The eradication therapy completely revealed the symptoms of 16 patients in the ulcer group (64%), 13 patients in the gastroduodenitis group (36%, P=0.03 vs. ulcer patients), 10 patients with erosive gastroduodenitis (52%), but this was only temporary. One year after the eradication therapy seven of the ulcer patients (28%), 11 patients with gastroduodenitis (31%) and seven patients with erosive gastroduodenitis (37%) were symptom-free. Most of the patients had epigastric pain (44%), heartburn (43%) and/or abdominal distension (33%). Nine ulcer patients (36%), 10 patients with gastroduodenitis (28%) and five patients with erosive gastroduodenitis (26%) were taking H(2)-blockers regularly. CONCLUSION: the 1-month post-eradication UBT was probable true negative in all of the evaluated cases, since 79 patients (98.75%) were also negative after 1 year. The Hp recurrence rate is very low (1.25%) in a 1-year period. The symptoms were relieved shortly after eradication therapy in the majority of patients with ulcer disease or erosive lesions. However, significantly smaller portion of the patients with gastroduodenitis became symptom-free. Only about one third of the treated patients remained symptom-free 1 year after the eradication.

Vesicular monoamine transporters in the rat stomach.

Cellular distribution of vesicular monoamine transporters (VMATs), known to regulate vesicular storage and release of biogenic amines (i.e., catecholamines, serotonin, histamine, etc.), have been studied in the rat stomach using in situ hybridization histochemistry (ISHH) and immunohistochemical (IHC) techniques. 35S-UTP labeled riboprobes showed that mRNAs of both VMATs are expressed in the gastric mucosa. A combination of ISHH and IHC verified that most of the parietal cells (among other epithelial cells) express mRNA of the peripheral type transporter (VMAT1) while enterochromaffin-like cells (ECL) of the fundic mucosa express mRNA of the central type (VMAT2). In addition, with double fluorescent IHC we detected VMAT1 protein in serotoninergic enterochromaffin cells (EC) of the stomach and in gastrin producing G cells of the antral mucosa. Similarly to the fundus, VMAT2 protein was present in ECL cells and in the enteric plexus. Surprisingly, serotonin- and/or histamine-containing cells in the connective tissue compartments of the stomach (i.e., lamina propria and submucosa), immunoreactive for a mast cell specific antigen, displayed neither VMATI nor VMAT2 immunoreactivity. Distribution of VMATs in the rat stomach support our previous observations on aminergic properties of two important gastrointestinal (GI) epithelial cell populations primarily known for other specific secretory products, i.e. dopaminergic properties of acid producing parietal cells and histaminergic properties of gastrin producing G cells. These data emphasize the existence of a non-neuronal, intrinsic aminergic system in the GI tract.

13C-Urea breath test is superior in sensitivity to detect Helicobacter pylori infection than either antral histology or rapid urease test.

There is no single technique which fulfils the criterion for a reference method to detect Helicobacter pylori (Hp) infection. The aim was to compare the results of antral histology (H), rapid urease test (U) and urea breath test (UBT) from antral biopsy samples in patients having gastric or duodenal lesions during upper GI endoscopy. We used the following methods: 1) biopsy specimens for histology (Warthin-Starry staining); 2) rapid urease test; and 3) 13C-urea breath test with infrared spectrometry. The total number of patients was 166 examined by H, U, and UBT. H, U and UBT were negative (-) in 64 patients and positive (+) in 51. The true positivity and false negativity (%, number of patients in parentheses) of each method based upon the positivity of the other two tests were: H+, U+ (54): UBT+, 94.4% (51) and UBT-, 5.6% (3); H+, UBT+ (57): U+, 89.5% (51) and U-, 10.5% (6); U+, UBT+ (65): H+, 78.5% (51) and H-, 21.5% (14). If Hp infection is considered to be positive when at least two tests detect the presence of Hp, UBT shows the highest sensitivity in comparison to histology of biopsy specimens and urease test. UBT is highly recommended as a screening test for Hp infection in patients presenting upper GI endoscopic alterations.

Gastrointestinal immunology: cell types in the lamina propria--a morphological review.

Defense mechanisms--including immune responses--of the gastrointestinal (GI) system rely on a delicate balance of multidirectional interactions of different components of the GI mucosa. The majority of the cells involved in immune reactions are in the lamina propria (LP) and in the submucosa. Several biologically active substances (enzymes, neurotransmitters, humoral mediators) and their receptors have been reported to be present in LP cells. These cells are in close morphological connections with the surface epithelial cells and with the surrounding vessels and nerve fibers, suggesting a functional association with them. In this paper cell types of the LP will be reviewed from a morphological aspect. In summary, LP cells can be classified as basic structural elements (fibroblasts, fibrocytes, vascular endothelial and smooth muscle cells), blood cells (granulocytes, mast cells, macrophages, T and B lymphocytes, plasma cells), and occasional epithelial and endocrine cells of the surface epithelium. Nerve fibers and terminals, but not neuronal perikarya, can also be seen in the LP. The appearance and the proportion of LP cells strongly depend on the functional activity of the GI system at any given time. Their number and distribution might be significantly altered in certain pathological conditions (infections, inflammations, ulcerations, and other GI disorders). We hope, this review may help clinicians, pathologists, and researchers in the recognition of LP cell types, and in demonstrating their activation, migration and proliferation in different physiological and pathological conditions.

Colocalization of somatostatin receptor sst5 and insulin in rat pancreatic beta-cells.

Somatostatin, also known as somatotropin release-inhibiting factor (SRIF), is secreted by pancreatic delta-cells and inhibits the secretion of both insulin and glucagon. SRIF initiates its actions by binding to a family of six G protein-coupled receptors (sst1, -2A, -2B, -3, -4, and -5) encoded by five genes. Messenger RNA for both sst2 and sst5 have been reported in the rat pancreas, and the sst2A receptor protein has been localized to rat pancreatic alpha and pancreatic polypeptide-secreting cells in the islets as well as to pancreatic acinar cells. In this study we have used double immunostaining to show that the sst5 protein is expressed exclusively in the beta-cells of rat pancreatic islets and localizes with insulin-secreting alpha-cells. The sst5 receptor is not colocalized with sst2A. Thus, in the rat SRIF inhibits pancreatic insulin and glucagon secretion via different sst receptor subtypes.

Non-neuronal dopamine in the gastrointestinal system.

1. Dopamine (DA) is a protective agent in the gastrointestinal (GI) tract in both rats and humans. Therefore, we have studied the site of DA production in rat and human GI tract using a variety of techniques, including immunocytochemistry (ICC), in situ hybridization histochemistry, reverse transcription-polymerase chain reaction, HPLC, western blotting and immunoelectron microscopy. 2. We found very high concentrations of DA that persisted after chemical sympathectomy (CS) in the gastric juice, the stomach mucosa and in the pancreas. Both the stomach mucosa and the pancreas also had tyrosine hydroxylase (TH) activity, most of which remained after CS. Double-labelling ICC showed that acid-producing parietal cells and the exocrine pancreas must also be capable of producing DA. 3. We isolated rat stomach parietal cells by cell fractionation and found that both DA and TH activity are present in isolated (denervated) parietal cells. These cells also have other features of aminergic cells: they are immuno- (and mRNA) positive for the DA plasma membrane transporter and vesicular monoamine transporter(s). In both gastric and duodenal mucosa, we demonstrated the presence of significant amounts of the D5 receptor that could serve as a target for locally produced DA. 4. Because DA, its biosynthetic enzymes and its transporters are also found in parietal cells in the human stomach, a mucosal protective system involving DA could be important clinically.

[Beneficial effect of the ACE inhibitor captopril in normotensive patients with insulin-dependent diabetes]. / Az ACE-gátló captopril kedvezö hatása normotenziós, inzulindependens cukorbetegekben.

The increase of glomerular filtration can often be observed in patients with insulin dependent diabetes mellitus, even in the early stage of the disease and it does not require the presence of microalbuminuria. This phenomenon can be explained by vasoconstriction occurring in the efferent arterioles. Eighteen normotensive, diabetic patients (aged: 28-42) who developed increased glomerular filtration were recruited in this study. The specific objectives were: 1. to study the beneficial effect of angiotensin converting enzyme inhibitor on the glomerular filtration, 2. to evaluate the effect of this treatment on blood pressure and hemodynamic parameters in normotensive, diabetic subjects. After a placebo period of one week, patients were treated orally a daily dose of 3 x 6.25 mg of captopril for twelve weeks. Glomerular filtration was assessed by the isotopic clearance method and blood pressure recordings were taken every 30 minutes throughout a day using an automatic programmable device. Preload, afterload and linear ejection fraction were estimated by echocardiograph, whereas cardiac index was measured by isotopic first pass technique. At the end of the treatment period a significant decrease of glomerular filtration was observed (from 141.9 +/- 10 ml/min to 98.9 +/- 12 ml/min; p < 0.01. Similarly, the afterload exhibited a significant drop due to drug treatment (45.6 +/- 5.8 x 10(3) dyn/cm2 vs. 55.4 +/- 4.7 x 10(3) dyn/cm2 at the end of the placebo period (p < 0.01). However, preload, linear ejection fraction, and cardiac index did not significantly change during the treatment. According to the results obtained from this study a beneficial effect of captopril on the early development of the glomerular hyperfiltration was demonstrated in normotensive diabetic patients who did not develop microalbuminuria. This issue needs to be investigated further in a large scale clinical trial.

Gastrin-producing endocrine cells: a novel source of histamine in the rat stomach.

Gastrin and histamine both potently stimulate secretion of acid into the gastric lumen. How these agents interact and how their release is controlled is poorly understood. Therefore, we decided to look for histamine in the antral portion of the rat stomach where the gastrin-producing G cells are located. We used immunocytochemical methods to visualize histamine, histidine decarboxylase (HDC, the enzyme that converts histidine to histamine), and the type 1 vesicular monoamine transporter (VMAT1, the protein responsible for moving histamine into vesicles for storage and release). We were surprised to find that histamine, HDC, and VMAT1 were all present in G cells. Our results suggest that G cells synthesize and secrete gastrin and histamine. Whether histamine acts in concert with gastrin to stimulate acid secretion, or functions as an autocrine inhibitor of gastrin release remains to be seen.

Dopamine produced by the stomach may act as a paracrine/autocrine hormone in the rat.

Dopamine (DA) has been suggested to be a protective factor in the gastrointestinal tract but neither a source of DA nor its exact targets of action have been identified. In this study, we demonstrate high levels of DA (and DOPA) which persist after chemical sympathectomy in the gastric juice of rats. Immunostaining and in situ hybridization histochemistry reveal the presence of tyrosine hydroxylase (TH), DA transporter and vesicular monamine transporters in the acid-producing parietal cells. Like DA, TH enzyme activity remains after chemical sympathectomy. We also demonstrate active reuptake and storage of DA that indicates a regulated release of this neurohormone from parietal cells. DA D1b receptor mRNA is the most abundant DA receptor subtype in gastric and duodenal epithelium. Therefore, we suggest that selective DA D1b receptor agonists may be useful adjuncts in the treatment of duodenal and gastric ulcers. Gastric epithelia possess the hallmarks of functional DA neuroendocrine cells, suggesting that DA has an important role in self-protective mechanisms of the gastrointestinal tract. These findings should allow elucidation of DA role in normal and disease states in the stomach and duodenum.

Cell specific expression of the sst2A and sst5 somatostatin receptors in the rat anterior pituitary.

Somatostatin (SRIF), originally described as a hypothalamic hormone that inhibits the release of growth hormone was subsequently shown to inhibit the secretion of multiple pituitary hormones. Five genes encoding six different SRIF receptors (sst1, 2A, 2B, 3, 4 and 5) have been cloned and mRNAs for all five are expressed in the anterior pituitary. We used double immunostaining to determine which cells in the anterior pituitary bear sst2A and sst5 receptors. Our results show that these two receptors are widely distributed in the pituitary gland and are both present in a large percentage of GH cells. In addition, sst5 occurs in a small population of corticotrophs and a large percentage of lactotrophs whereas sst2A is found in only a few lactotrophs but a large number of corticotrophs. The sst2A receptor is also expressed in about a third of the gonadotrophs and thyrotrophs. Interestingly, sst2A and sst5 receptors colocalize in a small percentage of cells, most likely somatotrophs demonstrating that the same cells can contain multiple sst receptor subtypes. These results indicate that sst subtype specific analogs are likely to be useful for the selective regulation of individual pituitary hormones.

Substantial production of dopamine in the human gastrointestinal tract.

Considerable urinary excretion of dopamine metabolites indicates that large amounts of dopamine are produced in unknown locations of the body. This study assessed the contribution of mesenteric organs (gastrointestinal tract, spleen, and pancreas) to the total body production of dopamine in humans and examined the presence of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, in gastrointestinal tissues. Blood sampled from an artery and portal and hepatic veins in eight subjects and from arterial and renal venous sites in other subjects was analyzed for plasma concentrations of dopamine and its metabolites. The activity and distribution of tyrosine hydroxylase was also examined in tissue samples from the stomach and duodenum. Higher concentrations of dopamine and its metabolites in portal venous than arterial plasma indicated substantial production of dopamine by mesenteric organs (12.0 nmol/min) amounting to 42-46% of the renal removal of circulating dopamine metabolites. Tissue samples showed immunoreactive tyrosine hydroxylase in nonneuronal cell bodies and detectable levels of tyrosine hydroxylase in nonneuronal cell bodies and detectable levels of tyrosine hydroxylase enzyme activity. The results show that mesenteric organs produce close to half of the dopamine formed in the body, most of which is unlikely to be derived from sympathetic nerves but may reflect production in a novel nonneuronal dopaminergic system.

Immunohistochemical localization of somatostatin receptor SST2A in the rat pancreas.

Somatostatin (SRIF) acts on specific membrane receptors to inhibit exocrine and endocrine pancreatic functions. Five SRIF receptor genes have been cloned, producing six receptor proteins (sst-s). We used a recently developed antibody to localize the sst2A splice variant in the rat pancreas. Western blots identified the sst2A receptor as an 90 kDa glycosylated protein in pancreatic tissue. In tyramide-amplified immunostainings all acinar cells, and the glucagon and pancreatic polypeptide immunoreactive cells (A and PP, respectively) were intensely labeled for sst2A, while no signal was detected in SRIF producing (D) cells. A very few insulin immunoreactive (B) cells were also labeled for sst2A, but the signal in these cells was lower than in exocrine, A or PP cells. Absorption of the sst2A antibody with the receptor peptide abolished specific staining in both immunoblots and tissue sections (negative control). These studies are the first to localize any SRIF receptor subtype in the rat pancreas. The specific localization of sst2A receptor in acinar, A and PP cells if confirmed in humans, would suggest that subtype specific analogs will be useful for the therapeutic regulation of exocrine and/or endocrine pancreatic secretion.

Tyrosine hydroxylase assay for detection of low levels of enzyme activity in peripheral tissues.

A nonisotopic assay for tyrosine hydroxylase, with optimized signal-to-noise ratios, enables determination of low levels of enzyme activity in peripheral tissues. DOPA produced by the enzyme is measured using HPLC with electrochemical detection. Increased signal-to-noise ratios are obtained by including in the reaction mixture glycerol for reduction of blank values and dihydropteridine reductase and NADPH for regeneration of the tetrahydropteridine cofactor. With this method, tyrosine hydroxylase activity can be detected in as few as 200 PC12 cells and in peripheral tissues at levels as low as 4.5 fmol/min/mg wet weight. The assay permits activity to be assessed in a variety of peripheral tissues.

Immunohistochemical localization of somatostatin receptor SST2A in the rat pancreas.

Somatostatin (SRIF) acts on specific membrane receptors to inhibit exocrine and endocrine pancreatic functions. Five SRIF receptor genes have been cloned, producing six receptor proteins (sst-s). We used a recently developed antibody to localize the sst2A splice variant in the rat pancreas. Western blots identified the sst2A receptor as an 90 kDa glycosylated protein in pancreatic tissue. In tyramide-amplified immunostainings all acinar cells, and the glucagon and pancreatic polypeptide immunoreactive cells (A and PP, respectively) were intensely labeled for sst2A, while no signal was detected in SRIF producing (D) cells. A very few insulin immunoreactive (B) cells were also labeled for sst2A, but the signal in these cells was lower than in exocrine, A or PP cells. Absorption of the sst2A antibody with the receptor peptide abolished specific staining in both immunoblots and tissue sections (negative control). These studies are the first to localize any SRIF receptor subtype in the rat pancreas. The specific localization of sst2A receptor in acinar, A and PP cells if confirmed in humans, would suggest that subtype specific analogs will be useful for the therapeutic regulation of exocrine and/or endocrine pancreatic secretion.

Distribution of somatostatin receptor messenger RNAs in the rat gastrointestinal tract.

BACKGROUND & AIMS: The gastrointestinal (GI) tract is a major source and target of somatostatin (SRIF). Recently, five pharmacologically different SRIF receptors (sst1-5) were cloned. The cellular and tissue distribution of the sst1-5 messenger RNAs (mRNAs) were studied in the rat GI tract using in situ hybridization histochemistry (ISHH). METHODS: Two sets of (35)S-uridine triphosphate (UTP)-labeled antisense and sense riboprobes were prepared for each sst. ISHH was conducted on frozen tissue samples from rat stomach, duodenum, jejunum, ileum, colon, and pancreas. RESULTS: mRNAs of all five sst-s are widely expressed in the rat GI tract. The distribution pattern for each sst mRNA was identical with both antisense probes. No specific signal was found with any of the sense probes. Each layer of the different parts of the gut expressed mRNAs of multiple sst subtypes. All organs expressed sst3 mRNA very intensely. The lowest levels of mRNA expression for all five subtypes within the GI tract were found in the pancreas. CONCLUSIONS: The widespread expression of sst mRNAs suggests a significant role for SRIF in the regulation of GI function.