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)

Some neurochemical changes in the gut of rats after five weeks of alloxan-induced diabetes were investigated. It was found that at this stage of diabetes the changes were restricted mainly to the small intestine with a special selectivity for the duodenum. No changes were found in the most part of the large intestine and rectum. The methionine-enkephalin content was markedly reduced throughout the small intestine, while vasoactive intestinal polypeptide was increased in duodenum, ileum and caecum. Substance P content was unaffected, while at later stages of the disease it was significantly reduced in the entire small intestine. Sympathetic noradrenaline and intrinsic serotonin contents were significantly increased in the duodenum and unchanged throughout the rest of the intestine. These data suggest that the small intestine and caecum might be the early target of diabetic autonomic neuropathy, that might involve progressively the rest of the large intestine at later stages as recent results have suggested. It is likely that the gastrointestinal dysfunctions, often present in diabetic patients, might also be due to the combined pre-synaptic alterations, and to the functional imbalance between Gs and Gi/Go transduction proteins recently reported. Insulin therapy, begun seven days after alloxan treatment, reduced drastically the hyperglycaemia, restored normal body growth and prevented all the gut neurochemical changes associated with alloxan-induced diabetes.
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PMID:Early neurochemical changes in the autonomic neuropathy of the gut in experimental diabetes. 128 97

We have studied the involvement of sensory nerves containing substance P (SP) in the modulation of stress-induced catecholamine (CA) secretion from the sympathetic nervous system and adrenal medulla. Adrenaline and noradrenaline (NA) levels were measured in blood samples withdrawn from the inferior vena cava (i.v.c.) at 5 or 15 min intervals for periods of up to 60 min, in adult rats during stress induced by insulin or cold. Insulin stress caused a biphasic elevation of plasma CA. Previous studies from our laboratory have shown that the first phase lasting 30 min is neurogenic, and the second phase from 30 to 60 min is non-neurogenic in mechanism. In control adult rats (with normal levels of SP in their splanchnic nerve), insulin stress caused a slow and progressive secretion of adrenaline into the circulation for the first 30 min (neurogenic phase). In the period 30-60 min (non-neurogenic phase) plasma adrenaline and NA levels rose at a much higher rate. In capsaicin-pre-treated rats (in which SP levels in the splanchnic nerve were depleted by 68%) insulin stress produced a steady increase in plasma adrenaline levels for up to 5 min similar to that in insulin-stressed control animals; however, by 10 min the plasma adrenaline levels had fallen to basal and remained low up to 30 min. From 30 to 60 min, plasma adrenaline and NA levels rose steeply as seen with control animals. We conclude that capsaicin pre-treatment affected the neurogenic phase but did not affect the non-neurogenic phase. Cold stress increased the plasma adrenaline levels by a neurogenic mechanism over 30 min in control rats. In contrast, in capsaicin-pre-treated, cold-stressed rats, plasma adrenaline did not increase significantly. Plasma NA levels were also significantly lowered in capsaicin-pre-treated, cold-stressed rats during the neurogenic phase but NA increases were not dependent on an intact adrenal innervation. The results using both insulin stress and cold stress suggest that capsaicin-sensitive (sensory) nerve fibres in the adrenal medulla and in sympathetic ganglia are capable of modifying the secretory responses of these tissues to stress. Results from our previous in vitro work are compatible with the view that SP may be the neuromodulator released from such sensory nerves to produce these effects. This suggests that the previously reported ability of SP to modulate nicotinic receptor function in vitro by either inhibiting the nicotinic response or protecting against nicotinic desensitization may be more than a mere pharmacological curiosity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of sensory fibres in the rat splanchnic nerve in the regulation of adrenal medullary secretion during stress. 242 Sep 73

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

The gastro-entero-pancreatic (GEP) endocrine system of a stomach-containing and of a stomachless teleost, Sparus auratus and Barbus conchonius, respectively, are studied immunocytochemically using different antisera against mammalian hormones. Insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP)-immunoreactive cells are identified in the endocrine pancreas of both species. Only the distribution of PP-immunoreactive cells differed strongly; in the principal islet of both fishes, few PP-immunoreactive cells are present, whereas in the smaller ones many of them are observed in S. auratus and none in B. conchonius. In the digestive tract of S. auratus 10 endocrine cell types can be distinguished: neurotensin-, secretin-, serotonin-, somatostatin-, and two types of substance P-immunoreactive cells exclusively in the stomach, and C-t-gastrin/CCK-, glucagon-, Met-enkephalin-, PP-, and only one type of substance P-immunoreactive cells in the intestinal epithelium. With the exception of substance P-immunoreactive cells, the other four intestinal endocrine cells, as well as an unspecific immunoreactive cell, can also be found in B. conchonius. Coexistence of glucagon- and PP-like immunoreactivity is observed in the pancreas of S. auratus and in the gut of B. conchonius. Pancreatic and gut endocrine cells showing only PP- or glucagon-like immunoreactivity are found, too.
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PMID:A comparative immunocytochemical study of the gastro-entero-pancreatic (GEP) endocrine system in a stomachless and a stomach-containing teleost. 288 63

Effects of regulatory molecules on growth of mouse pancreatic acinar cells in culture were examined. The cholecystokinin (CCK) analogue caerulein and cholecystokinin octapeptide (CCK-8) each led to threefold increases in incorporation of [3H]thymidine into DNA. Gastrin, which interacts weakly with the CCK receptor, stimulated DNA synthesis, but only at much higher concentrations. In contrast, other secretagogues that utilize Ca2+ as an intracellular messenger, including carbachol, bombesin, substance P, and the ionophore A23187, did not induce trophic responses. Factors that affect intracellular cAMP concentration, such as secretin, somatostatin, VIP, DBcAMP, and forskolin, did not increase DNA synthesis in cultured pancreatic cells. Insulin and epidermal growth factor induced two- and threefold increases in [3H] thymidine incorporation into DNA, respectively. The effects of insulin were mediated via insulin-like growth factor I receptors. Steroid hormones had little effect on pancreatic acinar cell DNA synthesis. The stimulatory effects of CCK, insulin, and EGF were additive. The combination of caerulein, EGF, and insulin in a hormonally defined medium led to a tenfold increase in the incorporation of [3H]thymidine into DNA. These data indicate that CCK, EGF, and insulin directly increase DNA synthesis in pancreatic acinar cells.
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PMID:Stimulation of pancreatic acinar cell growth by CCK, epidermal growth factor, and insulin in vitro. 302 Sep 92

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

We studied the actions of substance P, bombesin, vasoactive intestinal peptide (VIP), and the octapeptide of cholecystokinin (CCK-8-S) on the release of somatostatin, insulin, and glucagon from the isolated perfused pancreatico-duodenal canine preparation. Substance P at concentrations ranging from 0.2-5.0 nM stimulated the secretion of somatostatin, insulin, and glucagon in a dose-dependent manner. However, the responses evoked by substance P were modified by the prevailing glucose level; higher somatostatin and insulin and lower glucagon responses were obtained at the high glucose concentration of 8.3 mM rather than at the low glucose concentration of 2.8 mM. At a glucose concentration of 5.5 mM, somatostatin release was above the prestimulation level in response to 1 nM substance P (89 +/- 15%; P less than 0.01), VIP (49 +/- 7%; P less than 0.01), or CCK-8-S (99 +/- 21%; P less than 0.01); bombesin was without effect (16 +/- 14; P = NS). Insulin release was enhanced by substance P (150 +/- 45%; P less than 0.05), bombesin (162 +/- 56%; P less than 0.05), VIP (44 +/- 5%; P less than 0.01), and CCK-8-S (190 +/- 17%; P less than 0.001). Furthermore, a significant release of glucagon was evoked by 1 nM substance P (501 +/- 158%; P less than 0.05), bombesin (30 +/- 10%; P less than 0.05), VIP (43 +/- 8%; P less than 0.01), or CCK-8-S (140 +/- 19%; P less than 0.001).
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PMID:Effects of substance P and other peptides on the release of somatostatin, insulin, and glucagon in vitro. 615 61

The purpose of this study was to determine the effects of the vasoactive perivascular neuropeptide substance P (SP) on the growth and function of vascular endothelial cells in serum-free culture conditions with cells quiescent in the G0-G1 phase of the cell cycle and to characterize the response. In addition, interactions between SP and other growth factors and neuropeptides including insulin, platelet factors, neurokinin A, neurokinin B, and calcitonin gene-related peptide (CGRP) were studied on endothelial cell growth and compared. Growth effects were determined by stimulation of tritiated thymidine incorporation into DNA and cell proliferation. SP exhibited differential effects on cell growth that were a function of concentration, incubation time, interaction with other growth factors, and cell culture conditions. DNA synthesis in response to SP showed a bell-shaped distribution with a maximal effect that was 10.5-fold over control at 500 micrograms/mL of SP after 48 hours of incubation. The effect showed marked synergism with insulin (10 micrograms/mL) and with CGRP (0.01 to 10 micrograms/mL), which is colocalized with SP in vivo. Insulin and CGRP alone had no significant effect on endothelial cell growth. Furthermore, no synergism was observed between SP and platelet-derived growth factor or platelet-derived endothelial cell growth factor. Endothelial cell proliferation increased in response to SP to 2.6-fold over control at 48 hours, was maximal at 10 micrograms/mL SP, and also demonstrated synergism with insulin (10 micrograms/mL). Our studies indicate that neuropeptides play a significant role in regulating endothelial cell growth and proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth-promoting effects of substance P on endothelial cells in vitro. Synergism with calcitonin gene-related peptide, insulin, and plasma factors. 752 4


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