Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence suggests that of calcitonin (CT) and parathyroid hormone (PTH) is controlled by factors other than the ambient serum calcium concentration. We studied the effects of infusions of four neuroendocrine modulators upon CT and PTH levels: isoproterenol (beta-adrenergic agonist), methoxamine (alpha adrenergic agonist), prostaglandin E2, and somatostatin. Isoproterenol was a consistent secretagogue for both hormones. Maximal CT increments during isoproterenol infusion in normal subjects were 13 +/- 2 pg/ml (mean +/- SEM, n = 6, P less than 0.001; basal, 26 +/- 5). Maximal increments in PTH were 113 +/- 22 pg/ml (P less than 0.01, n = 6; basal, 430 +/- 11). Infusions of methoxamine increased CT by 13 +/- 5 pg/ml (n = 5, P less than 0.05; basal, 43 +/- 13), but had no effect on PTH. The means of the maximal CT increments during isoproterenol (21 +/- 8 pg/ml) and methoxamine infusion (28 +/- 11 pg/ml) were not statistically different from those achieved by acute elevations of serum calcium levels within the physiological range (41 +/- 23 pg/ml). Infusions of somatostatin and prostaglandin E2 had no or only transient effects on basal or stimulated CT or PTH levels. Our data suggest that adrenergic input modulates CT and PTH secretion in humans independently of changes in serum calcium.
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PMID:Neuroendocrine modulation of calcitonin and parathyroid hormone in man. 4 60

To determine whether somatostatin inhibits glucagon secretion directly at the pancreatic level and to study quantitatively the relative effects of somatostatin on glucagon and insulin secretion, the effects of various concentrations of somatostatin on glucagon and insulin release from the in vitro perfused rat pancreas in response to arginine (14.2 mM), isoproterenol (2 mg/ml) and theophylline (10 MM) were studied. Glucagon and insulin responses to arginine were progressively inhibited by somatostatin over a concentration range from 0.1-100 ng/ml. At all doses, somatostatin caused greater inhibition of glucagon secretion than of insulin secretion. Approximately 4 ng/ml somatostatin reduced glucagon responses 50%, whereas 90 ng/ml was required to produce comparable inhibition of insulin responses. Glucagon responses to isoproterenol, an activator of adenylate cyclase, and to theophylline, a phosphodiesterase inhibitor, were completely abolished by 100 ng/ml somatostatin. Isoproterenol did cause insulin release in this system, but insulin responses to theophylline were diminished by somatostatin. The present studies thus indicate that somatostatin is a potent inhibitor of both glucagon and insulin secretion and indicate that it acts directly on the pancreatic alpha and beta cells. Glucagon secretion is approximately 20 times more sensitive to the inhibitory effects of somatostatin than is insulin secretion. Furthermore, the present results suggest that somatostatin may act by modifying cAMP-dependent systems rather than by altering cAMP levels.
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PMID:Inhibition by somatostatin of glucagon and insulin release from the perfused rat pancreas in response to arginine, isoproterenol and theophylline: evidence for a preferential effect on glucagon secretion. 111 81

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

beta-Adrenergic receptors on membranes prepared from L6 myoblasts, wild-type S49 lymphoma cells, and an adenylate cyclase-deficient variant (cyc-) of S49 lymphoma cells bind the agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) with high affinity. In each case the agonist [3H]HBI is associated with a larger complex than is the antagonist [125I]iodopindolol, and the binding of [3H]HBI can be inhibited by GTP. These observations suggest that there is an agonist-dependent association of the receptor with a guanine nucleotide-binding protein. The goal of the present experiments was to investigate the possibility that an interaction of beta-adrenergic receptors with the inhibitory guanine nucleotide-binding protein of adenylate cyclase was responsible for these observations. Treatment of S49 cells with pertussis toxin decreased the extent of pertussis toxin-catalyzed [32P]ADP-ribosylation of a 41,000-dalton protein, measured in vitro, and decreased the inhibition of adenylate cyclase activity observed in the presence of somatostatin or analogues of GTP. Isoproterenol-stimulated adenylate cyclase activity was potentiated following treatment of wild-type S49 cells and L6 myoblasts with pertussis toxin. Although the ability of receptors on membranes prepared from L6 myoblasts to bind the agonist [3H]HBI was not affected by treatment of cells with pertussis toxin, treatment of cyc- S49 cells with pertussis toxin markedly decreased the ability of receptors to bind [3H]HBI. The observed inhibition of the binding of the agonist [3H]HBI to beta-adrenergic receptors on membranes prepared from cyc- S49 cells after treatment with pertussis toxin could be explained by an interaction between beta-adrenergic receptors and the inhibitory guanine nucleotide-binding protein. Such an interaction may represent a mechanism through which stimulation of the activity of adenylate cyclase by beta-adrenergic receptors can be regulated or through which beta-adrenergic receptors can affect the activity of cyclic AMP-independent cellular processes.
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PMID:Interaction of beta-adrenergic receptors with the inhibitory guanine nucleotide-binding protein of adenylate cyclase in membranes prepared from cyc- S49 lymphoma cells. 284 25

This study examined the relationship between postnatal metabolic and hormonal changes and the accompanying rapid increase in mitochondrial adenine nucleotide content (ATP + ADP + AMP) in rabbit liver. The cytosolic NAD+/NADH concentration ratio, calculated from tissue pyruvate and lactate values, increased linearly 6.6-fold during the 1st postnatal h. The mitochondrial NAD+/NADH concentration ratio, calculated from tissue acetoacetate and beta-hydroxybutyrate values, increased 28-fold by 30 min postnatal. These changes in NAD+/NADH suggest that tissue oxygenation occurs rapidly and that oxygen supply rather than substrate supply is limiting for mitochondrial respiration in the immediate postnatal period. The normal increase in mitochondrial adenine nucleotide content that occurs within 2 h after birth was inhibited by hypoxia (5% O2). Glucagon stimulated the postnatal increase in mitochondrial adenine nucleotides but had no effect in combination with hypoxia. Both glucose and somatostatin injections inhibited the increase in mitochondrial adenine nucleotides and increased the insulin-to-glucagon ratio. Isoproterenol or dibutyryl cAMP stimulated, but propranolol did not inhibit, the normal increase in mitochondrial adenine nucleotide content. Phentolamine did not stimulate the postnatal accumulation of adenine nucleotides. In summary, the results show that the insulin-to-glucagon ratio is probably the most important hormone regulator of the rapid recompartmentation of adenine nucleotides into the mitochondrial matrix and that tissue oxygenation is strictly permissive for this hormone effect in the first 2 h after birth.
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PMID:Regulation of mitochondrial adenine nucleotide content in newborn rabbit liver. 289 2

Immunoreactive somatostatin (IRS) was identified in the male rat Harderian gland (HG) by radioimmunoassay. Tissue was extracted and a displacement curve performed; there were no significant differences between values obtained with serial dilutions of extracted tissue and those from purified somatostatin standard used in the radioimmunoassay. Basal values of HG-IRS were found to be in the nanomolar range (10.8 +/- 3.5 ng IRS/mg protein). Hypophysectomy did not change the HG-IRS but, in vivo growth hormone (GH) treatment led to a dramatic increase (6-7-fold) in the levels of IRS in the HG. Isoproterenol, a beta-adrenergic agonist, when administered in vivo significantly decreased the HG-IRS content. The effect of two different calcium channel blockers on the isoproterenol-induced decrease of HG-IRS was studied; no changes were observed with nifedipine but verapamil, injected one hour after isoproterenol administration, prevented the drop in HG-IRS levels. These data demonstrate the existence of IRS in a new location, the rat Harderian gland, and support a classical endocrine regulation for its tissue concentration.
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PMID:Identification of immunoreactive somatostatin in the rat harderian gland: regulation of its content by growth hormone, beta-adrenergic agonists and calcium channel blockers. 290 39

The involvement of G proteins in receptor mediated astroglial cAMP formation was studied. Isoproterenol or prostaglandin E2 stimulated adenylate cyclase of primary astroglial cells was inhibited by somatostatin. Preincubation of cells with increasing concentrations of islet activating protein (IAP) diminished somatostatin inhibition of adenylate cyclase. At an IAP concentration of 50 ng/ml somatostatin inhibition was completely abolished. Studies on IAP catalyzed 32P-ADP-ribosylation of astroglial cell particulate material revealed an incorporation of radiolabel into three polypeptides in the molecular weight range of 41,000-39,000 Dalton. Pretreatment of intact cells with IAP reduced radiolabeling of this molecular species in a concentration dependent manner. No further radiolabeling above background level was detectable after pretreatment of cultures with 10 ng IAP/ml or more. At present, the occurrence of at least three IAP substrates (G proteins) does not permit an identification of the somatostatin receptor coupled G protein. Rather, the finding reveals that astrocytes are endowed with multiple variants of GTP binding proteins likely to be coupled to different receptors.
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PMID:Multiple pertussis toxin substrates as candidates for regulatory G proteins of adenylate cyclase coupled to the somatostatin receptor in primary rat astrocytes. 290 73

Antisera and radioimmunoassays against five different regions of prosomatostatin (proSS) were used for chromatographical analysis and for immunohistochemical mapping of the products of proSS in the pig pancreas. Secreted products of proSS were studied by analysis of effluent from isolated perfused pig pancreas obtained during isoproterenol stimulation. All cells that were stained with one antiserum also stained with the other antisera. Immunoreactive nerves were not observed. Isoproterenol increased equally the secretion of proSS 20-36, proSS 65-76, and proSS 79-92 immunoreactivity. The major molecular forms identified in pancreatic extracts and released from the pancreas were proSS 79-92; proSS 65-76; an N-terminally extended form of proSS 65-76; and two larger forms comprising the proSS 20-36 sequence (but not the 1-13 sequence) with and without the proSS 65-76 sequence. ProSS 1-10, 1-32 and 65-92 (somatostatin 28) were not identified.
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PMID:Processing and secretion of prosomatostatin by the pig pancreas. 290 23

An animal model of diabetes mellitus has been developed in which neonatal rats are injected with streptozotocin at 2 days of age. After transient hyperglycemia followed by near normal glycemia, these animals develop nonketotic diabetes at about 6 wk of age that does not require insulin treatment. Secretion form the endocrine pancreas of 6-15-wk-old rats was evaluated with the isolated, perfused pancreas technique. Insulin secretion responded very poorly to high perfusate glucose concentrations, but in the presence of theophylline this meager response was enhanced. In contrast, arginine elicited an insulin response comparable to that of the control rats. Isoproterenol stimulated insulin secretion more in the diabetic model than in the controls, and tolbutamide failed to evoke insulin secretion. Glucagon secretion in response to arginine and isoproterenol was similar in both groups, but was suppressed less efficiently be glucose in the model than in controls. Evidence for enhanced basal secretion of somatostatin was also found. Thus, these hyperglycemic rats have a selective defect in glucose-stimulated insulin secretion with preservation of responses to other agents. In addition, abnormalities in the secretion of glucagon and somatostatin have been found.
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PMID:Islet secretion in a new experimental model for non-insulin-dependent diabetes. 611 5

The effects of adrenergic stimulation and suppression on somatostatin (SS), insulin, and glucagon release were studied in intact dogs. Isoproterenol, a beta-adrenergic agonist, significantly increased portal venous and arterial levels of SS and arterial levels of insulin and glucagon. Propranolol, a beta-adrenergic antagonist, significantly decreased portal venous SS and suppressed the isoproterenol-stimulated increases in the levels of SS, insulin, and glucagon. alpha-Adrenergic stimulation (propranolol plus epinephrine) decreased portal venous SS and arterial insulin. Phentolamine, and alpha-adrenergic antagonist, increased portal venous and arterial SS and arterial glucagon. These data suggest that in intact dogs, stimulation of beta-adrenergic receptors enhances the release of SS, insulin, and glucagon, while stimulation of alpha-adrenergic receptors inhibits the release of SS and insulin without having a definitive effect on glucagon.
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PMID:Adrenergic control of somatostatin release. 612 51


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