Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Particulate fractions of human small intestinal mucosa contain an enzyme capable of hydrolyzing N-benzoyl-L-tyrosyl-p-aminobenzoic acid (PABA-peptide), a substrate used for clinical purposes to assess exocrine function of the pancreas (PABA test, pancreas function test). In this paper we describe the purification of PABA-peptide hydrolase (PPH) by immunoaffinity chromatography using a monoclonal antibody (Mab), HBB 3/716/36, bound to protein A-Sepharose, and the characterization of the purified enzyme. The final preparation of the enzyme was in the immobilized form, i.e., bound to Mab-protein A-Sepharose, and showed a 765-fold enrichment over the mucosal homogenate. The enrichment factor in purified microvillus membranes was comparable to that of sucrase-isomaltase, a microvillar marker enzyme. This, together with immunoelectron microscopy using protein A-gold, indicated that PPH is located in the apical membrane of intestinal epithelial cells. The enzyme was found to be present throughout the small intestine with the activity in distal ileum being 4.5-fold higher than that in the proximal duodenum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoaffinity-purified PPH under reducing conditions revealed a polypeptide band with a relative molecular weight (Mr) of 100,000; under nonreducing conditions a major band with Mr 200,000 was observed. This indicates that PPH consists of two subunits with Mr 100,000 each, which are held together by one or more disulfide bonds. Two-dimensional polyacrylamide gel electrophoresis of the enzyme showed marked microheterogeneity, with pI's ranging from 6.0 to 6.85, probably due to glycosylation. The Km for PABA-peptide was 16.7 mM, and the pH optimum was 7.5-8.0 PPH activity was not inhibited by phenylmethylsulfonyl fluoride; pepstatin, leupeptin, amastatin, bestatin, puromycin, iodoacetate, or phosphoramidon. Activity was affected by captopril and Zinkov inhibitor, and in particular by thiol and chelating reagents. Chelator-inhibited PPH could be reactivated by bivalent metal ions, Zn2+ being the most effective. The enzyme catalyzed the hydrolysis of peptides including insulin B-chain, angiotensins I and II, bradykinin and bradykinin derivatives, oxytocin, and substance P, in each case yielding reproducible peptide fragments. On the basis of amino acid analysis of the products it could be concluded that peptides are hydrolyzed preferentially after an aromatic residue.
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PMID:N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase: a metalloendopeptidase of the human intestinal microvillus membrane which degrades biologically active peptides. 326 61

Calmodulin, a ubiquitous Ca2+-binding regulatory protein, is phosphorylated exclusively on tyrosine-99 in an insulin-dependent manner by wheat germ lectin-purified preparations of insulin receptors from rat adipocyte plasma membranes. Calmodulin is phosphorylated in the presence of polylysine, histone Hf2b, and protamine sulfate, but not in the absence of these cofactors or in the presence of other basic compounds known to interact with calmodulin, such as mellitin, myelin basic protein, chlorpromazine, trifluoperazine, substance P, glucagon, polyarginine, mastoparin, beta-endorphin, spermine, spermidine, and putrescine. The incorporation of 32P into calmodulin, expressed in terms of moles of phosphate per moles of calmodulin and assayed at calmodulin concentrations of 1.2 and 0.06 microM, is 0.023 + 0.002 and 0.046 + 0.006, respectively. This low stoichiometry is likely due to the relative impurity of the receptor preparation, as similar studies not shown here, using highly purified human insulin receptors, yield a stoichiometry of 1 mol phosphate/mol calmodulin. The time course of phosphorylation is characterized by a short initial lag phase of approximately 5 min, a rapid linear rate from approximately 5 to 40 min, with a steady state of 32P incorporation being approached at approximately 60 min. The K0.5 for ATP is 104 + 18 microM. Phosphorylated calmodulin is partially purified by HPLC on a C4 column using a trifluoroacetic acid/acetonitrile gradient solvent system. Phosphoamino acid analysis and limited thrombin digestion were used to determine that the site of insulin-induced phosphorylation of calmodulin is exclusively on tyrosine-99 regardless of the basic protein cofactor used. Phosphorylated calmodulin does not exhibit the characteristic Ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. Thus, the tyrosine phosphorylation of calmodulin represents a potentially important post-translational modification altering calmodulin's ability to regulate a variety of enzymes involved in growth, differentiation, and metabolic regulation.
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PMID:The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. 341 47

The gastroenteropancreatic (GEP) endocrine cells of the Japanese field vole were studied immunohistochemically. Somatostatin-, 5-hydroxytryptamine-, glicentin-, glucagon-, bovine pancreatic polypeptide-, gastrin-, gastric inhibitory polypeptide-, cholecystokinin-, substance P-, secretin-, neurotensin- and insulin-immunoreactive cells were revealed. The characteristic findings of the regional distribution and relative frequency of these immunoreactive cells in the GEP system of the vole were as follows. Somatostatin-immunoreactive cells were more numerous in the oxyntic glands than in the pyloric glands. Some somatostatin-immunoreactive cells were found in small clusters in the oxyntic glands. Gastrin-immunoreactive cells were detected not only in the pyloric glands and small intestine but also in the caecum and spiral colon. Gastric inhibitory polypeptide-immunoreactive cells were also detected in the pyloric glands and no motilin-immunoreactive cell was found in the gastroenteropancreatic system.
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PMID:Immunohistochemical study of gastroenteropancreatic endocrine cells of the herbivorous Japanese field vole, Microtus montebelli. 353 46

In mammalian tissues the C-terminal amide structure has been found to occur only in neuroactive or hormonally-active peptides. About half known neuropeptide and peptide hormones have this unique chemical feature. Using a chemical detection method, a search for previously unknown peptides that possess the C-terminal amide structure in extracts of brain and intestine was carried out and a number of novel neuropeptides and hormonal peptides, designated neuropeptide Y, PHI, peptide YY, galanin and neuropeptide K were isolated. We recently performed a similar search in porcine pancreas and found a high concentration of a peptide having a glycine amide at its C-terminus. Here we report the isolation, primary structure and biological activity of this novel peptide. The 49-residue peptide strongly inhibits glucose-induced insulin release from the isolated perfused pancreas and was therefore named pancreastatin. It may be important in the regulation of insulin secretion and in the pathogenesis and treatment of diabetes mellitus.
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PMID:Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. 353 10

Carcinoid tumors of the middle ear are rare, with only three previously reported cases. The authors report the light and electron microscopic and immunohistochemical features of two carcinoid tumors that occurred in a 34-year-old female and a 21-year-old male. Both presented with unilateral hearing loss. By light microscopic examination, both were characterized by trabecula of tall columnar cells with basal nuclei and no mitotic activity. Electron microscopic examination demonstrated large numbers of pleomorphic neurosecretory granules, perinuclear aggregates of intermediate filaments, cell junctions, and surface microvillous processes. Some cells contained intermediate filaments forming tonofilaments and lacked secretory granules. These cells stained for cytokeratin by immunoperoxidase and separated the neuroendocrine cells from the underlying basal lamina. The cells in this tumor stained for the molluscan cardioexcitatory peptide. Cells in both tumors also stained for pancreatic polypeptide. Neither case stained for lysozyme, insulin, glucagon, somatastatin, gastrin, substance P, thyroid-stimulating hormone, adrenocorticotropic hormone, Met-enkephalin, Leu-enkephalin, neuropeptide Y, peptide YY, neurotensin, Bombesin, serotonin, neuron-specific enolose, glial and neural filaments, S-100 protein, cholecystokinin, beta-endorphin, beta-human chorionic gonadotropin, luteinizing hormone/follicle-stimulating hormone, vasoactive intestinal polypeptide, prolactin or calcitonin. Carcinoid tumor of the middle ear can be distinguished from paraganglioma and middle ear adenoma.
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PMID:Carcinoid tumors of the middle ear. 357 33

We have examined the effect of the trophic protein, nerve growth factor (NGF), on organotypic cultures of fetal rat striatum. Treatment of cultures with NGF for 10-11 days resulted in a 5- to 12-fold increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT; EC 2.3.1.6). in a dose-dependent fashion. This effect was not elicited by insulin, ferritin, or cytochrome c, proteins similar in structure or physicochemical properties to NGF. The effect of NGF on CAT activity was specifically blocked by anti-NGF antiserum, whereas treatment with the antiserum alone did not have a significant effect on the enzyme. Immunocytochemical studies of the treated cultures, using a monoclonal antibody directed against CAT, revealed positively stained neurons exhibiting dendritic and axonal processes. NGF did not have an effect on total protein content of the striatal cultures, suggesting a highly specific effect. Moreover, levels of substance P, a peptide localized to other, noncholinergic neurons, were not altered by NGF. Substance P remained unchanged after treatment with NGF for 12 days, whereas CAT activity increased 12-fold in sister cultures. Although the mechanisms of action of NGF on striatal cholinergic interneurons remain to be determined, the marked, specific response of CAT suggests that this well-defined trophic protein may play a critical role in normal brain development.
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PMID:Nerve growth factor promotes cholinergic development in brain striatal cultures. 386 96

Intestinal adaptation has been studied in rats with pancreatic atrophy induced by feeding a copper-deficient diet and penicillamine and in rats with carbohydrate maldigestion induced by feeding of an alpha-glucosidase inhibitor (acarbose). Pancreatic atrophy led to a significant increase of weight, protein, and DNA content as well as specific activities and total amounts of the enzymes sucrase and maltase in the distal but not in the proximal part of the small intestine. Plasma levels of CCK and GIP were significantly higher in rats with pancreatic atrophy, whereas plasma levels of gastrin and insulin were lower. Tissue concentrations of gastrin in the antrum and GIP in duodenum and jejunum were unchanged. Duodenal CCK and jejunal substance P, somatostatin, and VIP and ileal substance P and somatostatin were significantly decreased in rats with acinar atrophy. Glucosidase inhibition by acarbose feeding led to weight increase of the small intestine and cecum. This was more marked when acarbose was fed together with a fiber-free diet. Under these conditions the protein and DNA content also increased significantly in both gut segments and maltase and sucrase content predominantly in the distal part. Insulin plasma concentration decreased significantly in the acarbose-fed groups, whereas GIP, gastrin, and CCK plasma concentrations remained unchanged. After fiber-rich diet tissue concentrations of gastrin in the antrum and insulin in the pancreas were significantly higher and GIP concentrations in the duodenum and jejunum significantly lower than after fiber-free diet. Acarbose increased the pancreatic insulin concentration only in the fiber-free group and did not influence gastrin and GIP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adaptation of the small intestine to induced maldigestion in rats. Experimental pancreatic atrophy and acarbose feeding. 389 54

Twenty-seven cases of medullary carcinoma of the thyroid gland (MCT) were studied by light microscopy, immunocytochemistry, and electron microscopy. Immunoreactivity for neuron-specific enolase (NSE) and calcitonin was present in all tumors. The numbers of peptides and serotonin demonstrated in each case varied from one to eight. Bombesin was present in 18 of the 27 cases, serotonin in 15, leu-enkephalin in 8, somatostatin in 8, gastrin in 3, substance P in 1, vasoactive intestinal peptide (VIP) in 1, and ACTH in 1. Insulin and glucagon were not encountered in any of the tumors. Immunoreactivity for thyroglobulin was seen in five primary tumors as well as in one lymph node metastasis. The finding of concurrent production of calcitonin and thyroglobulin within the same tumor is enough to question the dogma of the separate origin of follicular cells and C-cells. We were unable to attach any clinical importance to the production of multiple peptides and/or amines.
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PMID:Medullary carcinoma of the thyroid gland: an immunocytochemical study. 390 54

Pancreatic endocrine cells were stained immunocytochemically for insulin, glucagon, somatostatin and pancreatic polypeptide by the PAP technique or sequentially for two hormones by the PAP followed by an indirect immunogold procedure. Pancreatic endocrine cells of Chrysemys are found scattered as single cells or small aggregates throughout the exocrine parenchyma; only the splenic region shows islets consisting of a B cell core surrounded by a loose mantle of A cells and occasional D cells. PP cells were not found in this splenic portion but were found scattered throughout the remainder of the pancreas. In contrast to the typical vertebrate islet, Chrysemys pancreatic endocrine cells are characterized by a lack of preferential association of one cell type with another and suggests that paracrine regulatory mechanisms may not be operable in this species. Insulin secretion from pieces of Chrysemys pancreas has been measured in incubation and perifusion systems employing a heterologous radioimmunoassay. Insulin release by Chrysemys B cells is enhanced by elevated levels of glucose (300 mg/dl), however, response appears to be somewhat slower compared to other vertebrate B cells. Gastrin, secretin, neurotensin, motilin, serotonin, PYY, glucagon, gastric inhibitory polypeptide, somatostatin and insulin were demonstrated immunocytochemically in open-type GEP cells of the mucosal epithelium of the Chrysemys intestine. Of these cells, gastrin, neurotensin and insulin cells appear to be the most numerous while the other types appear less frequently. Cells containing PP, bombesin, cholecystokinin and substance P could not be demonstrated. The localization of insulin to GEP cells of the turtle intestine is an unusual finding but has been confirmed by radioimmunoassay of extracts of the intestinal mucosa.
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PMID:The gastro-entero-pancreatic system of the turtle, Chrysemys picta. 391 12

Peptides and non-peptides acting as vasoconstrictors or vasodilators have been tested in dog isolated carotid arteries with and without endothelium and in the presence and absence of a variety of antagonists and inhibitors of endogenous substances. It has been found that substance P and several other tachykinins, bradykinin, neurotensin, bombesin and acetylcholine relax the isolated artery only when the endothelium is present, while VIP, isopropylnoradrenaline, adenosine, histamine, prostaglandins E1 and E2, glucagon and insulin relax and angiotensin, vasopressin, oxytocin, 5-HT and noradrenaline contract the isolated vessel, no matter whether the endothelium is present or not. Peptide and non-peptide antagonists have been used with success to show that vasoconstrictors and vasodilators act on specific receptors, since their effects are reduced in the presence of antagonists, specific for one or another of the various agents. Inhibitors of the arachidonic acid cascade only reduce the effect of acetylcholine, suggesting that at least two different mechanisms are involved in the endothelium-mediated relaxation of arterial smooth muscles to peptide and non-peptide agents. The results summarised in this paper suggest that the site of action of several vasodilators is the endothelium, while other vasodilators and all the vasoconstrictors influence the arterial vessels tone presumably by acting on the smooth muscle cells.
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PMID:Effects of peptides and non-peptides on isolated arterial smooth muscles: role of endothelium. 393 Feb 67


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