UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with refractory diarrhoea (up to 10 l/d) following colectomy and ileostomy was treated with clonidine, after loperamide, tinctura opii, cholestyramine and somatostatin had failed to reduce stool volume to less than 6 l/d. Under combined treatment with clonidine (1200 micrograms/d) and somatostatin (6 mg/d), which was well tolerated, stool weights were normalised within 24 hours. This case report on the successful anti-diarrhoeic effect of clonidine is completed by experimental data from rat jejunal and duodenal segments. In the presence of the adenylate cyclase-stimulating agent forskolin, clonidine normalised both mucosal cAMP content and cAMP-induced hypersecretion in rat intestine. This suggests that the anti-diarrhoeic effect of clonidine in-vitro results from an alpha 2-receptor mediated inhibition of the stimulated adenylate cyclase. Case report and experimental data therefore support the theory that therapeutical application of clonidine in diarrhoea may be successful.
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PMID:[Treatment with clonidine in a case of the short bowel syndrome with therapy-refractory diarrhea]. 168 51

The mechanisms underlying the age-related decrease and increase in somatotroph responsiveness to growth hormone-releasing factor (GHRF) and somatostatin respectively were studied in rat pituitary membranes in vitro. Basal adenylate cyclase (AC) activity was similar in pituitary membranes from rats of 8 days (either sex) and male rats of 3 months, but it was almost threefold higher in membranes from male rats of 21-23 months. GHRF induced a lower percentage stimulation of AC activity in membranes from infant and old than adult rats. Somatostatin inhibited stimulation of AC induced by forskolin more effectively in membranes from adult than infant and old rats. In parallel experiments, since the tissue we used is formed by a mixed population of pituitary cells, we evaluated, for comparison, the effect on AC of neurohormones, i.e. vasoactive intestinal polypeptide (VIP) and dopamine which act primarily on lactotrophs. VIP induced a lower fold-stimulation of AC activity in membranes from infant and old than adult rats. Dopamine inhibited forskolin-induced stimulation of AC in the following rank order of magnitude: old, adult and infant rats, and was also more effective in inhibiting basal AC activity in old than in adult rats. The stimulatory and inhibitory G proteins (Gs and Gi) coupled to AC were measured indirectly by evaluating stimulatory and inhibitory effects of different concentrations of GTP on AC. GTP, at stimulatory concentrations, increased AC activity in membranes from infant and adult rats similarly whereas its effect was significantly greater in membranes from old rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age-related changes of growth hormone secretory mechanisms in the rat pituitary gland. 168 89

We examined the interaction between the stimulatory guanine-nucleotide-binding protein, Gs, and the inhibitory guanine-nucleotide-binding protein, Gi, in cell membranes of S49 lymphoma cells. In these cells, beta-adrenergic receptors stimulate the activity of adenylate cyclase via Gs, whereas inhibition via somatostatin receptors is transduced by an inhibitory G-protein, Gi. Using an antibody that selectively recognizes alpha s, the monomeric, but not the heterotrimeric, alpha-subunit of Gs, we quantified the extent of dissociation of Gs in a competitive e.l.i.s.a. Incubation of S49-cell plasma membranes with 0.1 microM-isoprenaline, 100 microM free Mg2+ and 100 microM-GTP produced substantial subunit dissociation of Gs, which was reversible by addition of purified beta gamma-subunit dimer or somatostatin. Somatostatin produced an immediate (without a lag) time- and concentration-dependent decrease in the concentration of dissociated Gs (kinhib. for somatostatin = 51 +/- 12 nM) and in the activity of adenylate cyclase (kinhib. = 121 +/- 20 nM). By contrast, after addition of a 10-fold molar excess of beta gamma-dimer relative to alpha s, there was a 2-3 min lag, after which the beta gamma-dimer re-associated Gs. Isoprenaline-induced dissociation of Gs was accompanied by a release of alpha s from the incubated membranes to a post-100,000 g supernatant, and somatostatin could reverse this release. Immunoblot analysis with both a C-terminal anti-peptide antibody and an antibody directed against a sequence near the N-terminal also showed release of alpha s by the beta-agonist and reversal by somatostatin. Membrane release of Gs by isoprenaline that could be blocked by somatostatin was also confirmed in reconstitution studies of supernatant fraction into cyc- S49-cell membranes. We conclude that in native cell membranes somatostatin-induced activation of Gi dissociates Gi and interferes with the Gs activation cycle by providing beta gamma-dimer, which acts to prevent or reverse formation of monomeric alpha s. Because alpha s can be released from the cell membrane, regulation of the local concentration of GTP-liganded dissociated alpha s is likely to be an important factor in modulating the activity of adenylate cyclase.
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PMID:Inhibition of subunit dissociation and release of the stimulatory G-protein, Gs, by beta gamma-subunits and somatostatin in S49 lymphoma cell membranes. 168

To characterize the intracellular mechanisms by which somatostatin modulates the insulin secretion, studies were performed with isolated rat pancreatic islets at 12 mmol l-1 glucose. Somatostatin (0.1-1000 nmol l-1) inhibited the glucose-induced insulin secretion concentration-dependently. Increasing intracellular cAMP concentration either with dibutyryl-cAMP (1 mmol l-1) or by the adenylate cyclase activator forskolin (20 mumol l-1) partly reversed the inhibition by somatostatin (100 nmol l-1). Neither somatostatin (100 nmol l-1) nor dibutyryl-cAMP (1 mmol l-1 were able to affect the low insulin secretion observed in the absence of extracellular Ca2+. To study cAMP-independent mechanisms of somatostatin, the experiments were performed with and without dibutyryl-cAMP (1 mmol l-1) present. Both somatostatin (100 nmol l-1) and the Ca(2+)-channel blocker verapamil (25 mumol l-1) inhibited the insulin secretion both with and without dibutyryl-cAMP present. An additional inhibition of the insulin secretion was observed when somatostatin was combined with verapamil in the absence, but not in the presence of dibutyryl-cAMP. We conclude that somatostatin inhibits the glucose-induced insulin secretion both by cAMP-dependent mechanism which requires extracellular Ca2+, and by cAMP-independent/verapamil-sensitive Ca(2+)-channel-dependent mechanism.
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PMID:The interaction between cAMP-dependent and cAMP-independent mechanisms in mediating the somatostatin inhibition of insulin secretion in isolated rat pancreatic islets. 168 88

Functional somatostatin (SRIF, somatotropin release-inhibiting factor) receptors were expressed in Xenopus oocytes after injection of RNA isolated from the anterior pituitary tumor cell line AtT20. SRIF receptors were detected by measuring the ability of SRIF to inhibit cAMP formation stimulated by beta 2-adrenergic agonists in individual oocytes. beta 2-Adrenergic receptors (beta 2ARs) were expressed in oocytes by coinjecting RNA prepared by in vitro transcription of a beta 2AR cDNA clone with the pituitary cell RNA. Uninjected oocytes do not express detectable levels of either beta 2ARs or SRIF receptors. In oocytes coinjected with AtT20 and beta 2AR RNA, on the other hand, isoproterenol treatment led to a 2- to 3-fold increase in cAMP levels, whereas cotreatment with SRIF reduced this accumulation by 50-60%. The SRIF precursor somatostatin-28 and the cyclohexapeptide agonist MK678 also inhibited cAMP formation, whereas the biologically inactive N-terminal 14-amino acid fragment of somatostatin-28 was ineffective. The ability to detect changes in cAMP levels in individual oocytes may provide a simple procedure for the expression cloning of SRIF receptor cDNAs and other receptors functionally coupled to stimulation or inhibition of adenylate cyclase.
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PMID:Expression of functional pituitary somatostatin receptors in Xenopus oocytes. 168 51

The increase in hormone-stimulated cyclic AMP accumulation observed in a variety of intact cells after chronic pretreatment with drugs that inhibit adenylate cyclase activity has been attributed to an increase in adenylate cyclase activity following withdrawal of the inhibitory drug. In NG 108-15 mouse neuroblastoma X rat glioma hybrid cells (NG cells) chronically treated with the muscarinic cholinergic agonist carbachol, we have found a significant decrease in the apparent degradation rate constant for cyclic AMP, in addition to an increase in the prostaglandin E1 (PGE1)-stimulated cyclic AMP synthesis rate in intact cells. In carbachol-pretreated NG cells that were stimulated with a maximally effective dose of PGE1, and that accumulated steady-state cyclic AMP concentrations fourfold or more higher than in control cells, the apparent rate constant for degradation was about 53% lower than the value for control cells. In carbachol-pretreated cells stimulated with a submaximal dose of PGE1 to yield a steady-state cyclic AMP concentration comparable to control cells, the apparent rate constant was 31% lower than the value for control cells. In S49 mouse lymphoma cells (S49 cells) chronically treated with an analog of the inhibitory agonist somatostatin, the first-order rate constant for cyclic AMP degradation in intact cells following isoproterenol stimulation was 29% lower than the value for control cells. Despite these changes in the kinetics of cyclic AMP degradation in intact NG cells and S49 cells, there was either no change or a minimal change (less than 10%) in phosphodiesterase activities assayed in extracts of cells chronically exposed to inhibitory drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased cyclic AMP degradation in NG 108-15 neuroblastoma X glioma hybrid cells and S49 lymphoma cells chronically treated with drugs that inhibit adenylate cyclase. 168 17

Receptors for the main neural (acetylcholine), hormonal (gastrin) and paracrine (histamine) secretory stimulants and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of histamine is mediated via an increase in adenylate cyclase activity, whereas the effect of acetylcholine and gastrin are mediated via an increase in cytosolic levels of calcium. Strong synergism between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways. Acetylcholine and gastrin are also capable of releasing histamine from the gastric mucosa, probably from ECL cells. The inhibitory effects of somatostatin and prostaglandin E on acid secretion are mediated by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, ultimately responsible for acid secretion. The intramural neural and paracrine pathways involved in the regulation of gastrin secretion in the antrum and acid secretion in the fundus have also been identified. Of prime importance is the somatostatin cell, which exerts a paracrine restraint on gastrin secretion and acid secretion. Elimination of this restraint or disinhibition is one of the mechanisms by which the stimulatory influence of cholinergic neurons is exerted on gastrin and parietal cells. Gastrin secretion is regulated by a cholinergic neuron that causes inhibition of somatostatin secretion and thus stimulation of gastrin secretion (disinhibition) and a noncholinergic neuron that causes direct stimulation of gastrin secretion by releasing the neurotransmitter, bombesin (or gastrin-releasing peptide). Acid secretion is regulated by a cholinergic neuron that causes direct stimulation of the parietal cell and indirect stimulation by decreasing somatostatin secretion, thus eliminating its inhibitory effect on the parietal cell (disinhibition). In addition, a regulatory feedback mechanism exists whereby intraluminal acidification stimulates somatostatin secretion, which in turn attenuates acid secretion. Gastric acid secretion may also be regulated by one or more intestinal inhibitory hormones, the most likely candidates being secretin, intestinal somatostatin, and neurotensin. Enterogastrone activity probably reflects the combined effect of all these hormones. Precise information on receptors and signal transduction mechanisms as well as on intramural neural and paracrine regulatory pathways has led to the development of new drugs capable of inhibiting acid secretion. These include antagonists that interact with stimulatory receptors (histamine H2-receptor antagonists, muscarinic receptor antagonists, and gastrin receptor antagonists), agonists that interact with inhibitory receptors (somatostatin and prostaglandin E analogues), and irreversible inhibitors of the luminal enzyme, H+K(+)-ATPase.
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PMID:Control of acid secretion. 169 38

Somatostatin (SS-14) is known as an antigrowth factor for a variety of cell types, including gastrointestinal mucosa, exocrine pancreas, lymphocytes, and some tumors. We have recently identified and biochemically characterized SS-14-binding protein on rat liver plasma membranes (S. E. Raper, P. C. Kothary, and J. DelValle, Gastroenterology 96: A408, 1989; P. C. Kothary et al., Digestion 46 (Suppl 1): 58, 1990). We hypothesized that SS-14 may affect liver growth as well and investigated cellular mechanisms of this phenomenon focusing on the second messenger cAMP. Freshly isolated rat hepatocytes were plated on tissue culture dishes coated with Matrigel (laminin, heparan sulfate, and type IV collagen). The medium was not supplemented with serum or hormones. Either dibutyryl-cAMP (1 mM) or isobutylmethylxanthine (IBMX, 0.1 mM) was added in the presence or absence of SS-14 (10 nM). DNA synthesis was estimated by the rate of [3H]thymidine incorporation into DNA and by the labeling index (an autoradiographic measurement of the number of labeled nuclei). SS-14 significantly inhibited both [3H]thymidine incorporation and labeling index of rat hepatocytes stimulated by dibutyryl-cAMP or IBMX. SS-14 also inhibited intracellular cAMP accumulation stimulated by IBMX. We conclude that SS-14 exerts at least part of its antiproliferative effects via the adenylate cyclase system. Further study using other signal transduction systems may yield more information about mechanisms of hepatocyte growth.
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PMID:Inhibitory effects of somatostatin on rat hepatocyte proliferation are mediated by cyclic AMP. 171 80

Altered osmotic pressure and somatostatin (SRIF) rapidly alter prolactin (PRL) release from the pituitary gland of the euryhaline teleost, the tilapia. The present studies were undertaken to determine whether altered osmotic pressure and SRIF influence cAMP metabolism in a manner that is correlated with the pattern of PRL release observed previously. Although PRL release is stimulated within 10-20 min when medium osmotic pressure is reduced, cAMP metabolism was not altered. However, following 1 hr of incubation in the presence of IBMX, cAMP accumulation was higher in PRL tissue exposed to medium of reduced osmotic pressure. This suggests that cAMP does not initiate an increase in PRL release in response to reduced osmotic pressure. By contrast, SRIF reduced the forskolin-stimulated increase in cAMP levels in a manner consistent with its rapid effects on PRL release. Moreover, the ability of SRIF to suppress the forskolin-stimulated increase in cAMP levels suggests that SRIF may act to render adenylate cyclase less responsive to direct stimulation by forskolin.
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PMID:Effects of osmotic pressure and somatostatin on the cAMP messenger system of the osmosensitive prolactin cell of a teleost fish, the tilapia (Oreochromis mossambicus). 171 2

Canine jejunal epithelial cells were isolated and maintained in short-term culture to study cholecystokinin (CCK) release. Sequential digestion of jejunal mucosa with collagenase and ethylenediaminetetraacetic acid was followed by counterflow elutriation to enrich CCK-containing cells. After 40 hours in culture on collagen-coated plates, 8.4% of the initially seeded cells were attached; 8.7% of them stained positive with a C-terminal CCK/gastrin antibody and 2.5% stained positive with a gastrin-specific antibody. Basal release of CCK into the culture medium amounted to 1.3% of total cell content over 105 minutes. Receptor-independent stimulation of protein kinase C by the phorbol ester beta-phorbol-12-myristate-13-acetate caused significant CCK release. The inactive form, 4 alpha-phorbol-12-myristate-13-acetate, had no effect. Activation of adenylate cyclase by 10(-5) mol/L forskolin evoked a 2.5-fold increase in CCK concentrations, which was completely abolished by 10(-8) mol/L somatostatin. L-phenylalanine stimulated CCK release at 20 and 50 mmol/L, whereas D-phenylalanine caused significant hormone output only at 50 mmol/L. L-tryptophan had no effect. Cholecystokinin release stimulated by L-phenylalanine was not influenced by the addition of either somatostatin or somatostatin antibody. In conclusion, a system of isolated canine jejunal epithelial cells was developed in short-term culture. This preparation proved suitable for the study of CCK release on a cellular basis.
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PMID:Cholecystokinin release from isolated canine epithelial cells in short-term culture. 172 60

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