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)

Mast cells of human skin, but not lung, adenoids, tonsils, or intestine, release histamine in response to substance P, vasoactive intestinal polypeptide, and somatostatin. The substance P receptor of skin mast cells is not of the NK-1, NK-2 or NK-3 subtypes of smooth muscle. Time course and calcium dependency of release by peptides differed from anti-IgE. With anti-IgE, the molar ratios of histamine:PGD2:LTC4 generated by skin mast cells was 1,000:25:2, whereas with substance P these ratios were 1,000:1:0.1. Similar results were obtained with the other neuropeptides. The ability of peptides to stimulate skin mast cell histamine release suggests a mechanism whereby their release from dermal nerve endings is coupled to changes in microvasculature.
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PMID:Interaction of neuropeptides with human mast cells. 246 22

This short review examines two examples of studies into the mechanisms of allergic responses which have particular relevance to inflammation research. The first is the ability of human skin mast cells, but not those derived from lung, adenoids, tonsils or intestine, to release histamine in response to stimulation by neuropeptides including substance P, vasoactive intestinal polypeptide (VIP) and somatostatin. The neuropeptide activation site does not appear to be a classical tachykinin receptor but rather a binding site of low affinity and low specificity capable of interacting with neuropeptides and compounds with similar physicochemical characteristics. In contrast to IgE-dependent activation, neuropeptide stimulation of skin mast cells induces a rapid release of histamine with minimal generation of PGD2 and LTC4. This pseudo-allergic reaction is thought to underlie the weal and flare response in the skin and may have a role in urticaria. The second example describes studies to elucidate the mechanisms of the late asthmatic response by use of a guinea-pig model. As in man, both early and late phase responses in the guinea-pig are inhibited by sodium cromoglycate whereas only the early response is inhibited by the beta-adrenoceptor stimulant drug salbutamol. Examination of bronchoalveolar fluid has shown a temporal relationship between an airways neutrophilia and the late response. However, pharmacological manipulation and the use of an anti-neutrophil serum has shown that these events are not interdependent. The role of the airways eosinophilia requires further investigation.
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PMID:Allergy or inflammation? From neuropeptide stimulation of human skin mast cells to studies on the mechanism of the late asthmatic response. 265 5

The arachidonate cascade of human or rat platelets were found to be modified by peptides (bradykinin, angiotensin I, angiotensin II, Asp1-Val5-angiotensin II-amide, somatostatin) and proteases (trypsin, kallikrein). The lipoxygenase pathway was not altered by angiotensin I, angiotensin II, trypsin and kallikrein, while the synthesis some of the cyclooxygenase products was selectively changed by these substances. Bradykinin and somatostatin resulted in an attenuated formation of 12-HPETE and 12-HETE - U shape dose response curve, at the same time the synthesis of cyclooxygenase metabolites was increased - bell shape dose response curve. Asp1-Val5-angiotensin II-amide increased the synthesis of lipoxygenase products and diminished the formation of TxB2. At the same time this peptide selectively induced the enzymatic release of PGD2 from platelets. These peptides and proteolytic enzymes might have physiologic significance in the "Ying-Yang" balance in one hand between lipoxygenase and cyclooxygenase metabolites and on the other between the proaggregatory and antiaggregatory substances released from platelets.
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PMID:The action of peptides and proteases on the arachidonate cascade of human and rat platelets. 288 Apr 82

The functional and biochemical characterization of rat bone marrow derived mast cells (RBMMC) confirms both species-related differences between rat and mouse bone marrow-derived mast cells (MBMMC) as well as mast cell heterogeneity in a single species. Such RBMMC have the staining characteristics of mucosal mast cells and contain the mucosal mast cell protease. The RBMMC release the preformed granule mediator beta-hexosaminidase both in response to immunologic stimulation with 200 ng Ag (net release 15.8 +/- 3.8%) and in response to 1 microM calcium ionophore A23187 (net release 21.8 +/- 6.8%). However, compound 48/80, substance P, and somatostatin did not induce mast cell degranulation. In experiments with optimal beta-hexosaminidase release, the RBMMC generated similar quantities of the newly formed arachidonic acid metabolites leukotriene C4 and PGD2 when stimulated with either Ag or calcium ionophore A23187. The RBMMC incorporate [35S]sulfate into proteoglycans consisting of 90% chondroitin sulfates and 10% heparin. The chondroitin sulfates were comprised of chondroitin 4 sulfate and chondroitin sulfate diB sulfated disaccharides in a ratio of 4/1. Although we show that RBMMC and MBMMC share a low histamine content, functional IgE receptors and unresponsiveness to cromolyn and selective secretagogues (compound 48/80, substance P, and somatostatin), we also provide evidence that RBMMC differ from MBMMC in their profile of newly generated mediators, preformed granule proteoglycan, and lack of proliferative response to mouse IL-3.
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PMID:Functional and biochemical characterization of rat bone marrow derived mast cells. 297 57

The influence of prostaglandins (PG) on central nervous system regulation of blood sugar homeostasis was studied in rats. Substances were injected into the third cerebral ventricle of anesthetized rats while rectal temperature and hepatic venous plasma glucose concentration were recorded. Stereotaxic microinjection of PGD2, E1, E2, and F2 alpha produced hyperglycemia and hyperthermia. The relative order of potency in hyperglycemia, PGF2 alpha greater than D2 greater than E1 greater than E2, was not consistent with that of hyperthermia, PGE2 greater than F2 alpha greater than E1 greater than D2, which suggests that hyperglycemia was a primary, not secondary, response to hyperthermia. Injection of PGF2 alpha caused a dose dependent (5-200 micrograms) increase in the hepatic venous plasma glucose level. Neither the injection of PGF2 alpha (50 micrograms) into the cortex nor into the systemic vein caused hyperglycemia. The injection of PGF2 alpha into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norephinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through the femoral vein completely prevented the increase of glucagon after administration of PGF2 alpha, although the increase of plasma glucose level was still observed. PGF2 alpha-induced hyperglycemia did not occur in adrenodemedullated rats. Intravenous injection of naloxone or propranolol did not affect the hyperglycemia, but phentolamine significantly prevented the hyperglycemic effect of PGF2 alpha. These results suggest that intraventricular PGF2 alpha affects the central nervous system to produce hyperglycemia by increasing epinephrine secretion from the adrenal medulla.
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PMID:Prostaglandins affect the central nervous system to produce hyperglycemia in rats. 347 43

The effects of PGE2 and PGD2 on gastric somatostatin and gastrin releases were investigated using the isolated perfused rat stomach. In the presence of 5.5 mM glucose, the infusion of PGE2 elicited a significant augmentation in somatostatin release, but suppressed gastrin secretion from the perfusate. On the other hand, PGD2 did not affect somatostatin release, although the gastrin secretion decreased significantly, the same as after PGE2 infusion. These results suggest that PGE2 and PGD2 may be important in the regulation of gastric endocrine function, but that PGD2 does not affect gastric somatostatin secretion.
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PMID:Effects of prostaglandin E2 and D2 on gastric somatostatin and gastrin secretion. 613 20

The effects of PGE1, PGE2 and PGD2 on somatostatin, insulin and glucagon secretions were investigated at various glucose concentrations using the isolated perfused rat pancreas. At glucose concentrations varying from 0 to 16.7 mM, PGE1 and PGE2 enhanced somatostatin release in a glucose dose-dependent manner. PGE1 did not significantly stimulate insulin secretion at glucose concentrations of 4.4 mM or less, but did at glucose concentrations of 8.8 mM or more, PGE2 augmented insulin release at 4.4 and 16.7 mM glucose, but not in the absence of glucose. Glucagon release was induced by PGE1 and PGE2 in a biphasic pattern with the maximal response in the absence of glucose. Like PGE1 and PGE2, PGD2 stimulated insulin and glucagon release in a glucose-related fashion. PGD2, however, was not capable of stimulating somatostatin release at various glucose concentrations even in the presence of 16.7 mM glucose. In conclusion, PGE1, PGE2, and PGD2 increase insulin and glucagon secretion in a glucose-dependent manner. PGE1 and PGE2 also stimulate somatostatin release, but PGD2 has no effect on somatostatin secretion at the doses studied.
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PMID:Different effects of prostaglandin E1, E2 and D2 on pancreatic somatostatin release. 615 34

Histamine-containing cells isolated from rabbit fundic mucosa were found in a small cell elutriation fraction (cells with diameter about 9-12 microns) enriched in mucus and endocrine cells and containing less than 1% mast cells (F1 cells). Gastrin (HG-17), pentagastrin and CCK-8 (C-terminal octapeptide of cholecystokinin) dose-dependently stimulated histamine release (EC50, respectively, 0.126 +/- 0.03, 0.92 +/- 0.15 and 0.211 +/- 0.025 nM) and somatostatin inhibited this release. PGE1, PGE2 and PGD2 alone were unable to enhance histamine release even at high concentrations but, when used in combination with gastrin of CCK-8, the release of histamine caused by these peptides was potentiated (about 1.5- to 2-fold). Carbachol also enhanced the liberation of histamine but with a weaker potency and efficacy than the gastrointestinal peptides (EC50: 1.50 +/- 0.06 microM). The use of specific muscarinic antagonists for M1-, M2- and M3-type receptors led us to conclude that an M1 receptor might be involved in the muscarinic-induced stimulation of histamine release. Activators of protein kinase C, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleyl-2-acetyl-glycerol (OAG) as well as the calcium ionophore, A23187, induced histamine release, whereas agents which increased intracellular cAMP content were devoid of effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurohormonal regulation of histamine release from isolated rabbit fundic mucosal cells. 769 7

The purpose of this study was to characterize changes in gene expression in the brain of a seasonal hibernator, the golden-mantled ground squirrel, Spermophilus lateralis, during the hibernation season. Very little information is available on molecular changes that correlate with hibernation state, and what has been done focused mainly on seasonal changes in peripheral tissues. We produced over 4000 reverse transcription-PCR products from euthermic and hibernating brain and compared them using differential display. Twenty-nine of the most promising were examined by Northern analysis. Although some small differences were observed across hibernation states, none of the 29 had significant changes. However, a more direct approach, investigating expression of putative hibernation-responsive genes by Northern analysis, revealed an increase in expression of transcription factors c-fos, junB, and c-Jun, but not junD, commencing during late torpor and peaking during the arousal phase of individual hibernation bouts. In contrast, prostaglandin D2 synthase declined during late torpor and arousal but returned to a high level on return to euthermia. Other genes that have putative roles in mammalian sleep or specific brain functions, including somatostatin, enkephalin, growth-associated protein 43, glutamate acid decarboxylases 65/67, histidine decarboxylase, and a sleep-related transcript SD464 did not change significantly during individual hibernation bouts. We also observed no decline in total RNA or total mRNA during torpor; such a decline had been previously hypothesized. Therefore, it appears that the dramatic changes in body temperature and other physiological variables that accompany hibernation involve only modest reprogramming of gene expression or steady-state mRNA levels.
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PMID:Gene expression in the brain across the hibernation cycle. 1023 10

Although the interleukin (IL)-1 receptor is densely distributed in the leptomeninges constituting the blood/cerebrospinal fluid barrier, its physiologic significance has remained unclear. In the present study, we show that in cultured leptomeningeal cells, IL-1beta, tumor necrosis factors, or lipopolysaccharide causes a prominent increase in the synthesis and release of prostaglandin (PG) D synthase, which catalyzes the final step in the biosynthesis of PGD2. Although significant increases in the amount of PGD synthase were also observed with cells exposed to somatostatin, thrombin, or ciliary neurotrophic factor, these were much smaller than were those induced by the proinflammatory cytokines. Other agents tested including IGF-I had no effect upon the enzyme levels in the culture media. Furthermore, we found that the increased secretion of PGD synthase by IL-1beta was completely inhibited by 10(-7) M PGE2. The same dose of PGD2 or 15-deoxy-Delta(12-14)PGJ2 had no effect upon the IL-1beta action. In addition, PGE2 increased the level of fibronectin and eliminated the expression of zonula occludentes-1, a tight junction-associated protein from cultured cells, effects likely reflecting a loss of barrier integrity. These results demonstrate the importance of inflammatory stimuli as a physiologic regulator of the leptomeningeal cell function.
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PMID:Effects of interleukin-1beta and prostaglandin E2 on prostaglandin D synthase production in cultivated rat leptomeningeal cells. 1508 10


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