Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three monoclonal IgG 2a antibodies were produced after immunization of mice with dispersed cells from a human mid-gut carcinoid tumor. Acetone-fixed cryosections of 57 primary and metastatic mid-gut carcinoid tumors as well as 2 hind-gut (rectal) carcinoids showed a conspicuous immunoreaction while a thymic carcinoid was essentially unstained with the antibodies. The 3 antibodies yielded a similar pattern of immunostaining. The immunoreaction comprised more than 95% of the carcinoid tumor cells, and it was more uniform and intense in primary tumors than in mesenteric, hepatic, and ovarian metastases of the mid-gut carcinoid tumors. Immunofluorescence studies on suspended carcinoid tumor cells showed that the antibodies bound to the surface membrane of the cells. The antibodies immunostained enterocytes of the small and large bowel, intestinal metaplasia of the stomach mucosa as well as colorectal adenocarcinomas. Endocrine pancreatic tumors producing vasoactive intestinal polypeptide, gastrin, somatostatin, and/or pancreatic polypeptide as well as the epithelium of pancreatic ducts were also stained with the antibodies, whereas a large number of other normal and abnormal human tissues, including benign and malignant insulinomas, were unreactive. The findings indicate that the antibodies recognize differentiation antigens on the carcinoid tumor cell surface preserved also on endocrine and nonendocrine cells of the normal bowel mucosa. The restricted tissue reactivity of the antibodies suggests that they may constitute useful tools in the histological characterization of carcinoid tumors. Further studies may reveal if they are applicable for immunolocalization and perhaps even immunotherapy of these neoplasms.
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PMID:Monoclonal antibodies raised against mid-gut carcinoid tumor cells. 236 42

Adult onset nesidioblastosis (AON) is an extremely rare entity associated with hypersecretion of insulin. Previous reports have demonstrated that the somatostatin analog, Sandostatin (SMS), will control the clinical symptoms induced by infantile nesidioblastosis. We hypothesized that insulin, C-peptide, and secondary peptide secretion from AON is provocable. We also hypothesized that SMS would suppress both basal and provoked primary and secondary peptide secretion in AON. To test this hypothesis, in a patient with AON, 13 gut peptide levels were determined at set intervals during provocative testing with a test meal, a calcium infusion, a secretin bolus, and a glucagon bolus. These tests were repeated under the influence of SMS. Insulin, C-peptide, and pancreatic polypeptide (PP) levels were elevated in the basal state. SMS suppressed all three peptides (mean 68%) (p less than 0.05). Basal fasting glucose rose by 65%, and glucose ratios were raised throughout all four tests. Insulin:glucose ratios decreased during SMS therapy. Insulin and PP secretion was increased by all four provocative tests (mean 458% and 665% above baseline, respectively). C-peptide was provoked by three tests (mean 204%). Peptides with normal basal values were also provocable. GRP and glucagon were provoked by secretin stimulation (182%, 186%, respectively). Calcium infusion stimulated CIP release by 372%. SMS suppressed the peak provoked peptide levels in all positive provocation tests (p less than 0.05). Peak provoked insulin values were decreased by 59%, C-peptide by 75%, and PP by 92%. Peak provoked glucagon, CRP, neurotensin, and GIP levels were decreased by 20%, 65%, 51%, and 73%, respectively. The patient has been maintained on SMS (25 micrograms bid) for 1 yr and has shown decreased insulin levels, normal glucose levels, and, at 1 yr, leads an asymptomatic normal life. SMS is able to suppress primary and secondary peptide secretion in both the fasting and provoked state. The long-term efficacy of SMS may be predicted by its ability to suppress primary peptide release during peak provocation.
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PMID:Adult onset nesidioblastosis: response of glucose, insulin, and secondary peptides to therapy with Sandostatin. 240 44

The distributions of gut hormones in the colon of Hirschsprung's disease were investigated by the peroxidase-antiperoxidase (PAP) immunohistochemical method. Three colonic segments (ganglionic, oligoganglionic, and aganglionic) were stained by the unlabeled antibody enzyme method. The immunoreactivity of vasoactive intestinal polypeptide (VIP) was found to be reduced in the oligoganglionic and aganglionic segments. Antisera to substance P and met-enkephalin demonstrated immunoreactive cells and fibers in the ganglionic segment, whereas these cells and fibers were almost completely absent in the oligoganglionic and aganglionic segments. A similar distribution was seen for the mucosal endocrine cells with somatostatin immunoreactivity. Antisera to neurotensin, motilin, bombesin, and cholecystokinin revealed no immunoreactivity in the normal colon or the three segments. The differences in these peptides between normal and impaired colonal segments may be one of the causes of colon constriction in Hirschsprung's disease.
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PMID:Immunohistochemical investigations of gut hormones in the colon of patients with Hirschsprung's disease. 240 61

The presence and distribution of regulatory peptides in nerves and endocrine cells of the stomach, intestine and rectum of a urodele amphibian, the mudpuppy, Necturus maculosus, was studied immunohistochemically in sections or whole-mount preparations of the gut wall. The effect of the occurring peptides on gut motility was studied in isolated strip preparations of circular and longitudinal smooth muscle from different parts of the gut. Bombesin-, neurotensin-, substance P- and VIP-like immunoreactivity was present in abundant nerve fibres in the myenteric plexus of both stomach, intestine and rectum. Single fibres or bundles were present in the circular muscle layer and in a well-developed deep muscular plexus in the intestine and rectum. Immunoreactive nerve cells were found in the myenteric plexus of the stomach, intestine (neurotensin only) and rectum. Gastrin/CCK-like immunoreactivity was observed only in a few fibres in stomach and rectum. Endocrine cells containing bombesin-, met-enkephalin-, gastrin/CCK-, neurotensin-, somatostatin- or substance P- like immunoreactivity were present in the mucosa. The effect of bombesin was an inhibition of the rhythmic activity in circular muscle preparations and in longitudinal muscle from the rectum, while longitudinal muscle from the stomach usually responded with a weak increase in tonus. Neurotensin, like-bombesin, was inhibitory on the spontaneous rhythmic activity of circular muscle throughout the gut, while the effect on longitudinal muscle was an increase in tonus. Met-enkephalin and substance P increased the tonus of all types of preparations, and often, in addition, initiated a rhythmic activity superimposed on this maintained tonus. VIP had a general inhibitory effect on the preparations, decreasing tonus and/or abolishing rhythmic activity. It is concluded that bombesin-, neurotensin-, substance P- and VIP-like peptides are present in nerves throughout the urodele gut and may have physiological functions in regulating the motility of the gut. The gastrin/CCK-like peptide present in nerves of the stomach and rectum may affect the function of these parts of the gut. The regulatory peptides present in endocrine cells may, perhaps with the exception of the somatostatin-like peptide, affect the motility humorally.
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PMID:Neuropeptides in the gastrointestinal canal of Necturus maculosus. Distribution and effects on motility. 241 14

Rats with streptozotocin-induced diabetes of 10 weeks' duration showed significant changes in the total content of somatostatin, substance P and vasoactive intestinal polypeptide in the stomach and small intestine compared with control animals. An increase (p less than 0.05) in the concentration and total content of gastric somatostatin and a decrease (p less than 0.05) in the concentration and content of gastric substance P were seen in the streptozotocin-treated rats. The increase in the vasoactive intestinal polypeptide (VIP) content (54%, p less than 0.05) and the decrease in the substance P content (35%, p less than 0.05) of the gut may contribute to the impaired intestinal motility observed in animals with experimentally produced diabetes. Both the diabetogenic effect of streptozotocin and the changes in regulatory peptide concentrations were prevented by injection of nicotinamide before streptozotocin suggesting that the changes did not arise from a non-specific toxic effect of streptozotocin upon gastrointestinal neurones and/or endocrine cells.
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PMID:Changes in the somatostatin, substance P and vasoactive intestinal polypeptide content of the gastrointestinal tract following streptozotocin-induced diabetes in the rat. 241 23

This study reports on a difference in the inhibitory action of the neuropeptides somatostatin and Met-enkephalin on acetylcholine (ACh) release from myenteric plexus-longitudinal muscle strips of guinea pig small intestine. Met-enkephalin (8.7 X 10(-8) M) inhibited ACh release evoked by either substance P (3.7 X 10(-8) M) or neurotensin (7.5 X 10(-11) M), and this inhibition could be reversed by naloxone (5 X 10(-8) to 5 X 10(-5) M). Neurotensin-induced ACh release was also sensitive to the inhibition by somatostatin. However, when tested in a dose range from 6.1 X 10(-8) to 6.1 X 10(-6) M, somatostatin was ineffective in reducing the efflux of ACh evoked by substance P. These observations provided evidence to support the view that inhibitory peptidergic neurons within the myenteric plexus modulate the activity of cholinergic neurons with a high degree of specificity and that both somatostatin and Met-enkephalin have distinct neuromodulatory functions in the gut.
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PMID:Inhibitory peptidergic neurons: functional difference between somatostatin and enkephalin in myenteric plexus. 241 98

Several neuropeptides, more or less related to their mammalian counterparts, are present in the enteric nervous system in fish, and may function as neurotransmitters, cotransmitters or neuromodulators in this system. Excitatory effects on fish gut smooth muscle are found with bombesin, substance P and neurotensin. VIP and bombesin are inhibitory in some preparations and metenkephalin and somatostatin give varying responses. Of the more closely studied neuropeptides, a bombesin-like peptide may be involved in a cofunction with acetylcholine in the excitation of gut motility. One or more tachykinins may be involved in different mechanisms controlling the gut motility, directly or indirectly via, e.g., serotonergic neurons. Bombesin, a tachykinin and VIP may control gastric secretion, and VIP may have vasodilatory functions as well as inhibitory functions on gut motility at least in some species.
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PMID:Neuropeptide functions in the fish gut. 242 Dec 64

We have developed procedures for dissociating neurons from the myenteric plexus of the small intestine of newborn rats and for growing those neurons in cell cultures for up to 3 months. Neurons in these cultures retain many of the differentiated properties of myenteric neurons in vivo. This is the first of a series of 3 papers describing those properties. In this paper, we describe the morphology of cultured neurons that we have observed with light and electron microscopy; we also describe the patterns of straining observed when immunocytochemical techniques were used to localize neurotransmitter candidates in the cultured neurons. Intracellular injections of a fluorescent dye, Lucifer yellow, revealed that many of the cultured neurons had morphologies similar to those of myenteric neurons in vivo. When thin sections of cultures were viewed in an electron microscope, many neurons were observed to have numerous small (40-60 nm), clear synaptic vesicles and/or large (80-150 nm), opaque-cored (p-type) vesicles. Synaptic profiles were most often observed on neuronal somata. Neurons containing immunoreactive serotonin, substance P, somatostatin, enkephalin, bombesin and gastrin/cholecystokinin were observed in about the same proportions as they occur in the intact myenteric plexus. Neurons containing immunoreactive vasoactive intestinal polypeptide were found in higher numbers than reported in vivo. Neurons containing immunoreactive neurotensin, secretin and glutamate decarboxylase were not observed. An antiserum directed against choline acetyltransferase stained 40-50% of the neurons. We conclude that myenteric neurons continue to express much of their normal differentiated properties even when they are removed from the gut, dissociated into a suspension of single cells and grown in culture. Such cultures will be useful for correlating the morphological, biophysical, pharmacological and synaptic properties of individual myenteric neurons and for testing the ability of altered environmental conditions to change those properties.
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PMID:Neurons dissociated from rat myenteric plexus retain differentiated properties when grown in cell culture. I. Morphological properties and immunocytochemical localization of transmitter candidates. 242 14

The gastrointestinal and respiratory tracts contain numerous regulatory peptides produced by and released from specialised epithelial cells and the organ innervation. This complex system of endocrine cells and nerves is generally called "the diffuse neuroendocrine system". Markers are now available which permit the visualisation of the diffuse neuroendocrine system or its individual components. These include antibodies to neuron-specific enolase, chromogranin, neurofilament triplet proteins, the brain protein S100 and antibodies to a variety of regulatory peptides. Peptides present in the gut and lung innervation include: vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), galanin, substance P, calcitonin gene-related peptide (CGRP), neuropeptide tyrosine (NPY), somatostatin and cholecystokinin (the latter two are also localised to endocrine cells of the gut). Bombesin-immunoreactivity is found in nerves in the gut and in endocrine cells of the foetal/neonatal lung. Neuropeptides of the gut and lung originate either from local neurons (e.g. VIP, PHI, galanin) or extrinsic neurons localised in sensory ganglia (e.g. substance P and CGRP) or the sympathetic chain (e.g. NPY). Recent studies point to the involvement of regulatory peptides in diseases of the gut and lung. These, together with detailed distribution studies, provide supportive data on the putative role of the peptides in the control of normal bowel and respiratory functions. The gastrointestinal and respiratory tracts were within the systems investigated by Feyrter during his original observations on the existence of specialised epithelial cells with a putative regulatory function (Feyrter, 1938). These "endocrine/paracrine" cells were found to be scattered in epithelial organs throughout the body. In fact, endocrine cells of the respiratory tract are frequently referred to as "Feyrter's cells". The term "regulatory peptides" was introduced as a generic term (Polak and Bloom, 1983) after the finding that active peptides are produced both by cells of the diffuse endocrine or APUD (amine precursor uptake and decarboxylation) system (Pearse, 1983) and autonomic/sensory nerves. These peptides are released into the circulation from endocrine cells or locally from nerve terminals or paracrine cells. The concept of "gut/brain" peptides was dispelled after the findings that the respiratory tract was provided abundantly with numerous active peptides produced by and released from mucosal endocrine cells and/or the innervation.
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PMID:Regulatory peptides of the gastrointestinal and respiratory tracts. 242 59

The frequency of occurrence of the adrenergic, cholinergic, 5-hydroxytryptamine (5-HT)-, substance P (SP)-, methionine-enkephalin (met-Enk)- and somatostatin (SOM)-immunoreactive fibres innervating the smooth muscle of the large intestine in Hirschsprung and control children was compared. It was observed a higher frequency of catecholamine-fluorescence, acetylcholinesterase-positive and SOM-immunoreactive fibres in the muscularis externa and muscularis mucosa of the aganglionic segment in Hirschsprung gut as compared to that in the sigmoid colon and rectum in controls. In contrast, the frequency of SP-, met-Enk- and 5-HT-immunoreactive fibres in the aganglionic segment in Hirschsprung gut was lower than that in the controls. Ultrastructurally the cholinergic and adrenergic fibres occurred more often in the aganglionic segment in Hirschsprung gut than in the controls. A treatment with 6-OHDA and a fixation by Tranzer and Richards technique was used to confirm the nature of the adrenergic fibres. The p-type fibres occurred infrequently in the aganglionic segment of Hirschsprung gut. The results suggest that the change in the frequency of the nerves containing inhibitory transmitters may play an important role in the pathogenesis of Hirschsprung's disease.
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PMID:Histochemical, immunocytochemical and ultrastructural data on the innervation of the smooth muscle of the large intestine in Hirschsprung's disease. 242 97


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