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)

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
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PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

Vasoactive intestinal peptide (VIP) is a potent and efficient stimulator of adenosine 3':5'-cyclic monophosphate (cAMP) accumulation in a human colon carcinoma cell line, HT 29. cAMP accumulation is sensitive to a concentration of VIP as low as 3x10(-12) M. Maximum VIP-induced cAMP levels were observed with 10(-9) M VIP and are about 200 times above the basal levels. Half-maximum cAMP production was obtained at 3x10(-10) M VIP. (125)I-Labeled VIP was found to bind to HT 29 cells; this binding was competitively inhibited by concentrations of unlabeled VIP between 10(-10) and 10(-7) M. Half-maximum inhibition of binding was observed with 2x10(-9) M VIP. Secretin also stimulated cAMP accumulation in HT 29 cells, but its effectiveness was 1/1000 that of VIP. The other peptides tested at 10(-7) M, such as insulin, glucagon, bovine pancreatic polypeptide, somatostatin, octapeptide of cholecystokinin, neurotensin, and substance P, did not stimulate cAMP accumulation. Prostaglandin E(1) and catecholamines stimulated cAMP production but were 1/2.3 and 1/5.5 as efficient as VIP, respectively. Another malignant cell line from the gut, the human rectal tumor cell line HRT 18, is also sensitive to VIP. In HRT 18 cells, VIP stimulated cAMP accumulation with a maximal effect at 10(-8) M; half-maximum stimulation was observed at about 10(-9) M. These results demonstrate the presence of VIP receptors in two malignant human intestinal cell lines (HT 29 and HRT 18) in culture and provide a model for studying the action of VIP on cell proliferation.
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PMID:Vasoactive intestinal peptide: a potent stimulator of adenosine 3':5'-cyclic monophosphate accumulation in gut carcinoma cell lines in culture. 20 77

GH4C1 cells are a clonal strain of rat pituitary tumor cells which synthesize and secrete prolactin and growth hormone. Somatostatin, a hypothalamic tetradecapeptide, inhibits the release of growth hormone and, under certain circumstances, also prolactin from normal pituitary cells. We have prepared [125I-Tyr1]somatostatin (approximately 2200 C1/mmol) and have shown that this ligand binds to a limited number of high affinity sites on GH4C1 cells. Half-maximal binding of somatostatin occurred at a concentration of 6 x 10(-10) M. A maximum of 0.11 pmol of [125I-Tyr1]somatostatin was bound per mg of cell protein, equivalent to 13,000 receptor sites per cell. The rate constant for binding (kon) was 8 x 10(7) M(-1) min(-1). The rate constant for dissociation (koff) was determined by direct measurement to be 0.02 min(-1) both in the presence and absence of excess nonradioactive somatostatin. Binding of [125I-Tyr1]somatostatin was not inhibited by 10(-7) M thyrotropin-releasing hormones. Substance P, neurotensin, luteinizing hormone-releasing hormone, calcitonin, adrenocorticotropin, or insulin. Of seven nonpituitary cell lines tested, none had specific receptors for somatostatin. Somatostatin was shown to inhibit prolactin and growth hormone production by CH4C1 cells. The dose-response characteristics for binding and the biological actions of somatostatin were essentially coincident. Furthermore, among several clonal pituitary cell strains tested, only those which had receptors for somatostatin showed a biological response to the hormone. We conclude that the characterized somatostatin receptor is necessary for the biological actions of somatostatin on GH4C1 cells.
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PMID:Characterization of functional receptors for somatostatin in rat pituitary cells in culture. 21 Jan 85

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.
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PMID:Radioimmunoassay in diagnosis, localization and treatment of endocrine tumours in gut and pancreas. 22 84

The data presented concern the chemistry and biology of cardiotrop peptides and proteins isolated by us from the hypothalamus. The molecular mechanisms of the effect of neurohormone "C" (NC) as well as of a new cardiotrop hexapeptide from cattle hypothalamus are discussed. In in vitro studies on homogenates NC has been found to inhibit greatly not only 3'--5'-cyclo-AMP phosphodiesterase activity of brain and heart but also 3'--5'-cyclo-GMP phosphodiesterase activity. NC has been shown to be bound to specific proteins and to the regulatory unit of cyclo-AMP-dependent histone kinase of brain. It seems to compete with cyclo-AMP for the same proteins and is considered to be a regulator of intracellular cyclic nucleotides. NC has been shown to be combined to specific proteins in brain with non covalent bonds. A new cardiotrop hexapeptide has been shown to be present in bovine hypothalamus and its chemical structure has been found to be Tyr-Leu-Gly-Arg-Pro-Gly-amide. The acetylated form of this hexapeptide, which may be also present in brain, is much more active. The radioimmunochemical experiments carried out with antiserum 744 (from prof. Schally) by us have confirmed the existence of this hexapeptide and other fragments of LH-RH in the bovine hypothalamus. The effect of this hexapeptide on cardiac function and metabolism has been compared with a number of polypeptides (luliberin fragments). The hexapeptide has been shown to have not only cardiotropic but also a hypoglycaemic effect. It enhances the secretion of insulin and counteracts the inhibitory action of somatostatin on the insular apparatus. The hexapeptide produces significant changes in the activities of phosphorylase a and b as well as in that of phosphoprotein phosphatases. It reduces the amount of kinines in blood. Certain fractions of substance P, have been shown to have cardiotrop actitivty--they increase the rate of blood leaving the heart. The organotrop effects of a number of peptide neurohormones are discussed in connection with the hexapeptide. The results obtained have shown that the mechanisms underlying the effects of the cardioactive substances found by us are quite different. The data presented show that in brain a number of chemical factors (mainly peptides) are formed, which are involved in the regulation of heart function.
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PMID:[Chemistry and biology of hypothalamic cardioactive proteins and peptides]. 22 93

Isolated pancreatic islets were used to determine whether substances of hypothalamic origin could directly influence the release of insulin and glucagon. Media in which various regions of the brain had been incubated were tested in the islet system, as were the synthetic peptides neurotensin and substance P, and the catecholamines, dopamine and norepinephrine. Substance(s) released from the ventromedial hypothalamic (VMH) segments in vitro inhibited insulin release and stimulated glucagon release from the islets. Incubates of ventrolateral hypothalamic (VLH) or cortex tissue failed to alter insulin or glucagon levels. The VMH medium retained these activities even after oxidation with K3Fe (CN)6, whereas the ability of the catecholamines to inhibit insulin release and stimulate glucagon release was eliminated by this treatment. Neurotensin and substance P (0.1 and 1.0 nmol/ml) inhibited insulin release while glucagon release was increased; however, radioimmunoassay indicated that these peptides were virtually absent from the VMH incubate. These results show that incubates of VMH contain substances which can inhibit insulin and stimulate glucagon release in vitro. They may influence the endocrine pancreas by way of the peripheral circulation although the possibility of their occurrence in or near the pancreas itself has not been excluded.
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PMID:Effects of hypothalamic factors on insulin and glucagon release from the islets of Langerhans. 32 54

The distribution of peptide hormone-like immunostaining in the gastrointestinal tract of 11 teleost species was investigated by immunofluorescence. Cells immunoreactive for somatostatin were found in the glandular epithelium of the stomach of four species and in the epithelium of the pyloric appendage of one species. The mid-gut epithelium contained cells reactive with antibodies to glucagon (three species), gastrin (five species), pancreatic polypeptide (five species), and substance P (two species). Cells immunoreactive for met-enkephalin were found in the epithelium of both the mid-gut and the stomach of six species. In six species in which the endocrine pancreas was investigated, insulin-, glucagon-, and somatostatin-like immunoreactivity was observed. Pancreatic polypeptide was definitely localised by immunostaining in cells of the endocrine pancreas of only one out of three species examined. Vasocative intestinal polypeptide-, neurotensin-, bombesin-, and enkephalin-like immunoreactivity was identified in the gastrointestinal nerve fibres in various species. In view of the considerable species variation found, caution should be exercised in generalising about the peptides present in the gastrointestinal tract of fish.
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PMID:Peptide hormone-like immunoreactivity in the gastrointestinal tract and endocrine pancreas of eleven teleost species. 38 3

It has been reported that Xenopsin, Neurotensin and Substance P change plasma glucagon and insulin levels when they are administered in vivo. In order to clarify whether these agents have a direct effect on glucagon and insulin secretion from the pancreas, the action of each substance was examined by using the rat pancreas perfusion technique. The results were as follows: The perfusion with 1 and 5 nmole/min of Xenopsin for ten minutes resulted in a significant but transient release within two minutes. Neurotensin did not show any stimulatory effect on glucagon release in the concentration of 1 or 5 nmole/min for ten minutes. However, Substance P lowered significantly the glucagon concentration in the perfusate in a similar concentration. None of these substances influenced significantly insulin release from the perfused pancreas. These findings suggest that the hyperglucagonemia caused by these three agents in vivo may not be attributed to the direct effect on the pancreatic A-cell.
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PMID:[Glucagon-releasing activity of xenopsin, neurotensin and substance P in the perfused rat pancreas (author's transl)]. 63 79

This study was undertaken to assess whether a hypothalamic extract has any direct metabolic action on adipose and muscle tissues. An acid bovine hypothalamic extract (HE) was tested for its effect on the utilization of D[U-14C]glucose by isolated rat adipocytes and rat hemidiaphragms. The HE was ineffective in stimulating the conversion of labeled glucose into CO2 and glycogen by rat hemidiaphragm. However, in isolated adipocytes, the HE had significant lipogenic activity. This lipogenic effect was independent of insulin and nonsuppressible by insulin antibodies. The dose-response curve was linear and saturable. That insulin and the HE were not additive at maximal concentrations suggests that they act through a common rate-limiting step, possibly a receptor site. Other hypothalamic substances tested (thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and substance P) showed no lipogenic activity. Somatostatin (6 microgram/ml) was an insulin potentiator but only when preincubated with the fat cells. It is concluded that the hypothalamic regulation of body weight may be mediated by a neurohumoral mechanism affecting adipose tissue stores.
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PMID:Effect of a bovine hypothalamic extract on glucose utilization by rat adipocytes. 66 59

The effects of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, substance P, somatostatin, and a partially purified hypothalamic extract on insulin secretion were tested both in vitro and in vivo. Only somatostatin and the hypothalamic extract affected insulin secretion. In vitro, somatostatin decreased glucose-stimulated insulin secretion by isolated islets and in vivo significantly reduced the rate of insulin output into the portal vein. The hypothalamic extract significantly stimulated insulin secretion in both systems. These effects in vivo were independent of glucose concentration. Islets preincubated for four hours responded better in vitro to the hypothalamic extract stimulation and the somatostatin inhibition.
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PMID:Neuroendocrine control of insulin secretion. 81 25


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