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)

The neuropeptide vasoactive intestinal peptide (VIP) has been shown to stimulate cyclic AMP accumulation in Leydig cells isolated from rat testis. The effect was dependent on time, temperature and cell concentration. At 15 degrees C, half-maximal and maximal stimulation were observed at about 1 and 100 nM VIP, respectively. The interaction was specific since an order of potencies chicken VIP greater than rat VIP greater than secretin greater than glucagon and no effect of neurotensin and substance P were obtained. The efficiency of VIP was lower in pubertal rats and then increased in young-adult and adult animals. These results together with the known presence of VIP in the testis support the idea that VIP may be involved in the regulation and function of Leydig cells during development.
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PMID:Characterization and age dependence of the stimulatory effect of VIP on cyclic AMP accumulation in rat Leydig cells. 283 54

We investigated the role of neuropeptides and adrenergic agonists in the regulation of intracellular 3',5'-cyclic adenosine monophosphate (cyclic AMP) contents in cultured Schwann cells from sciatic nerve of neonatal Sprague-Dawley rats. Of the neuropeptides examined, vasoactive intestinal polypeptide (VIP) and secretin markedly stimulated the accumulation of intracellular cyclic AMP in a time- and dose-dependent manner with half maximum at 3 and 12 min, and 2.8 X 10(-5) and 5.0 X 10(-5) M, respectively. While somatostatin, substance P, adrenocorticotropin (ACTH), beta-endorphin, and nerve growth factor (NGF) did not show any effect on cyclic AMP metabolism, isoproterenol (IP), norepinephrine (NE) and epinephrine (E) also markedly elevated the Schwann cell cyclic AMP concentration. The rank-order of potency of these adrenergic catecholamines on cyclic AMP accumulation was isoproterenol greater than norepinephrine greater than epinephrine. Simultaneous addition of VIP or secretin to the Schwann cell culture synergistically enhanced the norepinephrine-induced elevation of intracellular cyclic AMP. The effect of norepinephrine was antagonized by a selective beta 1-adrenergic antagonist but not by beta 2- nor alpha-adrenergic antagonists. These results suggest that VIP, secretin, and beta 1-adrenergic agonists alone or synergistically may play a part in the regulation of metabolism of Schwann cells mediated through a cyclic AMP-dependent mechanism.
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PMID:Peptidergic and adrenergic regulation of the intracellular 3',5'-cyclic adenosine monophosphate content in cultured rat Schwann cells. 285 16

High levels of BN/GRP are present in classic SCLC and lung carcinoids, whereas BN immunoreactivity is absent in variant SCLC, adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma cell lines. BN-like peptides are secreted from classic SCLC into the tissue culture medium. The secretion rate of BN-like peptides from cell line NCI-H345 was increased 3-fold by VIP (1 microM). Also, VIP increased the cAMP levels in cell line NCI-H345 by an order of magnitude. Therefore, SCLC cells have functional VIP receptors which regulate the secretion of BN-like peptides. Also, SRIF (100 nM) inhibits the VIP-stimulated increase in cAMP levels and secretion rate of BN-like peptides from SCLC cells. Because BN stimulates colony formation, VIP and/or SRIF may be able to alter the growth of SCLC cells. BN-like peptides are secreted from SCLC cells into the plasma. The levels of BN immunoreactivity in the plasma of SCLC patients with extensive disease is 2- to 40-fold greater than that of patients with limited disease. Secretin infusion into patients with extensive disease produces a transient increase (7-fold) in the plasma concentration of BN-like peptides. BN-like peptides are also present in the CSF of SCLC patients. When released from SCLC cells, BN-like peptides may interact with cell surface receptors. [Tyr4]BN binds with high affinity (Kd = 0.5 nM) to a single class of sites (1500/cell) on cell line NCI-H345. The carboxyl terminus of BN or GRP is essential for high-affinity binding activity. BN-like peptides elevate cytosolic Ca2+ levels as a result of increased phosphatidylinositol turnover. The putative BN receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P inhibits high-affinity [Tyr4]BN binding, the ability of BN to elevate cytosolic Ca2+ levels, and colony formation of SCLC cells. Therefore, BN receptor antagonists may serve as useful agents to inhibit the growth of SCLC.
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PMID:The release of bombesin-like peptides from small cell lung cancer cells. 285 97

[125I-Tyr]Somatostatin [( 125I-Tyr]SRIH) binding was found in 11 GH-secreting pituitary adenomas [Kd = 0.46 +/- 0.15 (+/- SE) nM; maximum binding, 165 +/- 35 fmol/mg protein). This binding was specific, since it was displaced by somatostatin-14 (SRIH-14), N-Tyr-SRIH-14, and SRIH-28. In contrast, a number of peptides and drugs not structurally related to SRIH, such as bombesin, dopamine, LHRH, met-enkephalin, naloxone, neurotensin, secretin, substance P, TRH, or vasoactive intestinal peptide, did not affect [125I-Tyr]SRIH binding. [125I-Tyr]SRIH specific binding also was found in PRL-secreting pituitary adenomas. The kinetic characteristics of the specific binding were similar to those of GH-secreting adenomas. However, maximal binding was one quarter that of GH-secreting adenomas (37 +/- 9 fmol/mg protein). In contrast, nonsecreting (chromophobe) tumors were devoid of any specific binding. Finally, in acromegaly, the density of [125I-Tyr]SRIH-binding sites in the adenomas was negatively correlated with plasma GH levels before surgery (r = -0.80). This suggests that somatostatinergic control is involved in GH secretion in acromegalic patients.
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PMID:Somatostatin receptors in human growth hormone and prolactin-secreting pituitary adenomas. 286 Jan 20

Somatostatin, the hypothalamic release-inhibiting factor, has been found to stimulate gluconeogenesis in rat kidney cortical slices. Stimulation by somatostatin was linear and dose-dependent. Other bioactive peptides such as cholecystokinin, gastrointestinal peptide, secretin, neurotensin, vasoactive intestinal peptide, pancreatic polypeptide, beta endorphin and substance P did not affect the renal gluconeogenic activity. Somatostatin-induced gluconeogenesis was blocked by phentolamine (alpha adrenergic antagonist) and prazosin (alpha1 adrenergic antagonist) but not by propranolol (beta adrenergic antagonist) and yohimbine (alpha2 adrenergic antagonist) suggesting that the effect is via alpha1 adrenergic stimuli. Studies on the involvement of Ca2+ revealed that tissue depletion and omission of Ca2+ from the reaction mixture would abolish the stimulatory effect of somatostatin. Furthermore, somatostatin enhanced the uptake of 45calcium in renal cortical slices which could be blocked by lanthanum, an inhibitor of Ca2+ influx. It is proposed that the stimulatory effect of somatostatin on renal gluconeogenesis is mediated by alpha1 adrenergic receptors, or those which functionally resemble alpha1 receptors and that the increased influx of Ca2+ may be the causative factor for carrying out the stimulus.
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PMID:Somatostatin: a metabolic regulator. 286 45

A large number of antisera mainly raised against mammalian hormones are tested immunocytochemically on the GEP-endocrine system of mouse and fish (Barbus conchonius). The endocrine pancreas of mouse and fish appeared to contain the same four endocrine cell types; insulin-, glucagon-, PP- and somatostatin-immunoreactive cells. In mouse about 13 GEP endocrine cell types are distinguished: 1. insulin-, 2. somatostatin-, 3. glucagon-, 4. PP-, 5. (entero)glucagon-/PP-like, 6. CCK-like, 7. substance P-, 8. neurotensin-, 9. VIP-, 10. gastrin-, 11. secretin-, 12. beta-endorphin-, 13. serotonin-immunoreactive cells. Based on this and a previous study at least 13 GEP endocrine cell types seems to be present in stomachless fish: 1-9 as described for mouse, 10. (entero)glucagon-like, 11. met-enkephalin, 12. VIP-like, 13. unspecific immunoreactive endocrine cells. Coexistence of glucagon and PP-like peptides is found in the gut and pancreas of mice and in the gut of B. conchonius. In mouse pancreas and fish gut, endocrine cells showing only PP- or glucagon-like immunoreactivity are found too. In mouse stomach some endocrine cells showing only PP-immunoreactivity are demonstrated. In the same region coexistence of C-t-gastrin- and FMRF-amide-immunoreactivity is found in endocrine cells. The importance of these phenomena are discussed. Enteric nerves immunoreactive with antisera raised against substance P and GRP are found in mouse, against somatostatin and met-enkephalin in both mouse and fish and against VIP in fish.
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PMID:Immunocytochemical identification and localization of peptide hormones in the gastro-entero-pancreatic (GEP) endocrine system of the mouse and a stomachless fish, Barbus conchonius. 287 13

The effects of various biologically active peptides on net jejunal water and electrolyte fluxes were studied in dogs in vivo. Vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), glucagon, gastrin, bombesin and neurotensin all had secretagogue activity, while methionine enkephalin stimulated net absorption. Somatostatin had no effect on net basal water and electrolyte transport, but inhibited glucagon-stimulated secretion. Secretin, calcitonin, substance P and pancreatic polypeptide (PP) did not have any effect on net water and electrolyte transport in the doses used in these experiments. The precise role played by these peptides in the control of intestinal transport has still to be determined. Studies in man have confirmed that food in the proximal small bowel stimulates secretion at sites remote from the application of food, and abnormal secretion of some peptides (e.g. VIP) has been associated with diarrhoea. Somatostatin has been used successfully to reduce the volume of certain types of secretory diarrhoea. Methods used in these experiments have been applied to the study of the composition and absorption characteristics of solutions used for oral rehydration in diarrhoea and in exercise-induced dehydration. Glucose polymers have been shown to be absorbed as rapidly as glucose from the jejunum.
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PMID:The effect of luminal and hormonal factors on small intestinal water and electrolyte transport. 287 15

The results of our investigations into the localization of Na+,K+-pump activity in pancreatic and parotid acinar cells and the effects of hormones and neurotransmitters on pump turnover can be integrated with data on other aspects of stimulus-response coupling to construct models of the neurohumoral control of protein, fluid, and electrolyte secretion (Fig. 23). In both tissues, Ca2+ and cyclic AMP serve as intracellular messengers. In pancreatic acinar cells, the Ca2+-dependent pathway activated by the occupation of CCK or cholinergic receptors provides the primary stimulus for digestive enzyme secretion. Cyclic AMP plays a comparatively minor role; VIP and secretin are much less effective stimulators of protein secretion. Conversely, cyclic AMP levels in parotid acinar cells, which are modulated primarily through occupation of beta-adrenergic receptors, are a major determinant of enzyme secretion. Activation of the Ca2+-dependent pathway by cholinergic or alpha-adrenergic agonists or substance P is less important. The presence of dual control processes in each gland suggests that the observed differences in effectiveness of cyclic AMP- versus Ca2+-dependent secretagogues may reflect not different mechanisms, but rather a shift in the relative emphasis placed on each pathway. This emphasis could conceivably result from subtle variations in the interaction between cellular protein kinases and phosphatases and their phosphoprotein substrates. Electrolyte secretion, on the other hand, appears to involve both discrete and common entities. In pancreatic acinar cells from rodent species, cholinergic or CCK receptor occupancy elicits a Ca2+-dependent increase in the open-state probability of nonselective cation channels in the basolateral plasma membrane. The resultant influx of Na+ and efflux of K+ is most probably the factor which activates Na+, K+-pumps. Based on electron probe studies of the effects of cholinergic agonists on acinar cell Na+ and K+ contents discussed earlier, a transient reduction in the intracellular K+/Na+ ratio of up to 4-fold may occur. A shift of this magnitude in the cytoplasmic microenvironment of the Na+, K+-pump clearly would have a stimulatory influence (see discussion by Jorgensen, 1980). In addition, Ca2+ itself may have direct effects on Na+,K+-pump activity. Calcium at levels much above 1 microM progressively inhibits Na+,K+-ATPase activity (Tobin et al., 1973; Yingst and Polasek, 1985). In unstimulated guinea pig pancreatic acinar cells, Ca2+i measured by quin-2 fluorescence was 161 +/- 13 nM (Hootman et al., 1985a) which increased to a maximal concentration of 803 +/- 122 nM following CCh stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroendocrine control of secretion in pancreatic and parotid gland acini and the role of Na+,K+-ATPase activity. 287 3

This study was undertaken to assess the prevalence and characteristic hormonal profile of endocrine cells in Barrett's mucosa and to determine to what extent this profile was shared by endocrine cells of adenocarcinomas arising therefrom. In addition, lower oesophageal carcinomas, not associated with columnar metaplasia, were examined to see if they exhibited a different hormonal profile. The patients studied comprised 43 who had had multiple oesophageal biopsies. 35 who had had oesophagogastric resection for adenocarcinoma arising in Barrett's mucosa and 26 in whom the resection showed no metaplastic epithelium adjacent to tumour. Argyrophil cells were present in 90% of biopsies and resections of Barrett's mucosa combined, irrespective of the histological type of metaplastic epithelium. By immunocytochemistry the most frequently identified substance in mucosal endocrine cells was serotonin (82%) followed by somatostatin (54%), secretin (22%) and pancreatic polypeptide (17%). Gastrin, bombesin, cholecystokinin, ACTH and substance P were not identified in metaplastic mucosa in any case. The difference in expression of serotonin by endocrine cells of tumours arising in Barrett's mucosa (31%) and those not (3.8%) was statistically significant (P less than 0.0186). Carcinoembryonic antigen (CEA) was demonstrated in 60% of oesophageal carcinomas, both endocrine positive and endocrine negative. Focal CEA expression was seen in 4.6% of biopsies and 14% of Barrett's mucosa adjacent to tumour. These results indicate a higher prevalence of endocrine cells in Barrett's mucosa than hitherto documented and suggest that serotonin may be a useful marker in distinguishing between primary oesophageal and putative gastric cancers at the gastro-oesophageal junction. The identification of CEA in oesophageal columnar epithelium is of little value in predicting the development of malignancy.
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PMID:The relationship of endocrine cells, dysplasia and carcinoembryonic antigen in Barrett's mucosa to adenocarcinoma of the oesophagus. 288 73

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


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