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)

Very low concentrations of somatostatin (S-14) strongly potentiate the in vitro aggregation induced by collagen, ristocetin and arachidonic acid, but not that induced by ADP or epinephrine, in both human platelet rich plasmas and gel-filtered platelet preparations. Desensitization phenomena may be induced either by repeated addition of S-14 or long lasting contact between S-14 and platelets.
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PMID:In vitro enhancement of human platelet aggregation by somatostatin. 290 69

Our previous study concerning guanine nucleotides regulation of labeled somatostatin binding has suggested that somatostatin receptors on pancreatic acinar cell membranes probably couple with the inhibitory guanine nucleotide regulatory protein (Ni). In order to clarify the possible role of Ni in mediating signal transduction of somatostatin in the pancreas, we further examined the effect of pretreatment with islet activating protein (IAP) on the inhibition of VIP-stimulated cellular cyclic AMP content by somatostatin in isolated rat pancreatic acini. Increasing concentrations of somatostatin decreased VIP-stimulated cellular content of cyclic AMP in the acini, with a maximal inhibition at 10(-8) M somatostatin. When pancreatic acini were pretreated with varying concentrations of IAP for 4 hours, the somatostatin-induced inhibition of cyclic AMP content was attenuated in a dose dependent manner by IAP pretreatment. Incubation of pancreatic acinar membrane with preactivated IAP and [32P] NAD resulted in labeling of a Mr = 41,000 protein band, consistent with alpha-subunit of Ni in many other cell types previously reported. On the other hand, a Mr = 41,000 protein band on SDS gel was reduced in a dose dependent fashion by IAP pretreatment, when acini were pretreated with increasing concentrations of IAP. These results suggest that only the Mr = 41,000 protein is a specific substrate in pancreatic acinar membranes for IAP-induced ADP-ribosylation. Furthermore, the reduction of 32P incorporation to Mr = 41,000 protein by IAP pretreatment occurred in parallel to decreases in somatostatin-induced inhibition of cellular cyclic AMP contents in pancreatic acini.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of islet activating protein on somatostatin-induced inhibition of cellular cyclic AMP content in isolated rat pancreatic acini]. 290 81

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

The possible effect of cholera toxin (CTX) on hormonal inhibition of adenylyl cyclase in somatostatin (SST)-sensitive GH3 cells was quantitatively evaluated. The toxin treatment employed led to an essentially complete ADP ribosylation of all alpha s subunits of the stimulatory regulatory component (Gs) of the system and to ca. 5- to 7-fold increases in the activity measured, yet it failed to affect the inhibitory action of SST regardless of whether analyzed in terms of degree of inhibition (ca. 60%) that is attainable or in terms of the apparent Kact with which the inhibitory hormone elicits its action. In absolute terms the activity inhibited after CTX was ca. 6 times larger than that inhibited under control conditions, indicating that SST is equally effective in regulating control and CTX-stimulated adenylyl cyclase system and that interpretations are independent of possible intramembraneous compartmentalizations of adenylyl cyclase and its various regulatory components. Since CTX-mediated ADP ribosylation of the alpha-subunits of Gs has been demonstrated to result in an at least 10-fold decrease in the potency (i.e. EC50) with which the beta gamma-complexes of G proteins act to stabilize preactivated purified alpha-subunits of Gs and in an approximately 300-fold decrease in the potency with which exogenously added beta gamma-complexes act to prevent activation of Gs in intact membranes, the present data indicate that beta gamma-complexes cannot be mediating the inhibitory effects of hormones by interfering with activation of the Gs of adenylyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibitory regulation of adenylyl cyclases. Evidence inconsistent with beta gamma-complexes of Gi proteins mediating hormonal effects by interfering with activation of Gs. 315 58

In the presence of cimetidine, pentagastrin and somatostatin prostacyclin formation does not differ significantly from the value obtained with the buffer control, whereas cimetidine alone is able to inhibit ADP-induced platelet aggregation in vitro to a small degree. It is concluded that the in vivo action of the drugs if not primarily mediated by prostacyclin.
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PMID:[Influence of cimetidine, pentagastrin and somatostatin on prostacyclin synthesis of gastric mucosa in vitro]. 610 73

The aim of the present study was to further evaluate the significance of circulating platelet aggregates induced by somatostatin in insulin-dependent diabetic subjects. Eight insulin-dependent diabetics and eight normals were infused with somatostatin at increasing doses (250, 500, and 750 microgram/h), each dose for 30 min. In diabetics, somatostatin induced the appearance in blood of platelet aggregates in a dose-dependent fashion, the highest level being observed with the highest dose (750 microgram/h), p less than 0.005). In normals, circulating platelet aggregates were detected only with the infusion of the highest rate of somatostatin (p less than 0.025). This effect of somatostatin was reversible, since it tended to disappear 30 min after the infusion was stopped. In six additional insulin-dependent diabetics, a previous infusion of phentolamine (0.5 mg/min) completely prevented the appearance of platelet aggregates by somatostatin. No significant variation of the aggregation response to both ADP and collagen and the platelet count was seen in both experiments. Somatostatin, as expected, reduced the basal concentration of plasma glucose, glucagon, and C-peptide in both diabetics and normals. On the basis of these results, we suggest that somatostatin has some proaggregating capacity in vivo, probably by interacting with adrenergic mechanisms.
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PMID:Further studies on the significance of circulating platelet aggregates induced by somatostatin in man. 611 Jan 60

The present study was undertaken to reevaluate the influence of somatostatin on platelet function in insulin-dependent diabetics and in normal subjects. In in vivo studies, nine insulin-requiring diabetics were infused with cyclic somatostatin (250 microgram/hour) for 120 minutes or with saline, in randomized order. This dose of somatostatin, sufficient to depress the basal concentrations of plasma glucose, glucagon and C-peptide, resulted in no significant change of platelet aggregation response to either ADP or collagen. By contrast, a progressive and significant reduction of platelet aggregation response to ADP was found during saline infusion. A similar pattern of response was seen in normal subjects. In all diabetics, but not in normals, somatostatin induced the appearance of circulating platelet aggregates. In in vitro studies, somatostatin augmented the aggregation response to epinephrine in both normals and diabetics. In conclusion, somatostatin counteracts the decrease of platelet aggregation response to ADP seen in saline studies, induces the appearance of platelet aggregates in diabetics and potentiates the aggregation response to epinephrine (in vitro) in both normals and diabetics. These actions of somatostatin suggest some aggregating capacity of the peptide in man.
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PMID:Circulating platelet aggregates induced by somatostatin in insulin-dependent diabetic subjects. 611 May 70

cyc--Variants of S49 lymphoma cells are defective in the stimulatory guanine nucleotide site of the adenylate cyclase but contain an inhibitory site. Treatment of cyc- cells with islet-activating protein (IAP), which causes ADP-ribosylation of an Mr 40 000 polypeptide in cyc- membranes, abolishes adenylate cyclase inhibition by GTP and the peptide hormone, somatostatin, but not that induced by GTP gamma S. Furthermore, somatostatin-induced stimulation of GTP hydrolysis is lost. Thus, the data indicate that IAP interferes with the adenylate cyclase system by an action at the inhibitory guanine nucleotide site.
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PMID:Adenylate cyclase inhibition and GTPase stimulation by somatostatin in S49 lymphoma cyc- variants are prevented by islet-activating protein. 613 42

Specific [125I]-Iodo-NTyr somatostatin binding sites are present in adenohypophyseal and cerebral cortical membranes. Guanine nucleotides reduce the maximal binding capacity of adenohypophyseal binding sites without significantly affecting their apparent affinity. In pituitary as well as in cortex, GTP is the most potent nucleotide followed by GDP and guanylyl imidodiphosphate (GMP-PNP). The effect appears specific of guanine nucleotides since ATP, ADP and AMP are inactive on [125I]-Iodo-NTyr somatostatin binding. These results, showing the nucleotide sensitivity of [125I]-Iodo-NTyr somatostatin binding in pituitary and cerebral cortex, are compatible with a coupling of somatostatin receptors with adenylate cyclase.
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PMID:Guanine nucleotide sensitivity of [125I]-Iodo NTyr somatostatin binding in rat adenohypophysis and cerebral cortex. 613 1

The inhibitory and stimulatory guanine nucleotide-binding regulatory components (Gi and Gs) of adenylate cyclase both have an alpha X beta subunit structure, and the beta subunits are functionally indistinguishable. GTP-dependent hormonal inhibition of adenylate cyclase and that caused by guanine nucleotide analogs seem to result from dissociation of the subunits of Gi. Such inhibition can be explained by reduction of the concentration of the free alpha subunit of Gs as a result of its interaction with the beta subunit of Gi in normal Gs-containing membranes. However, inhibition in S49 lymphoma cyc- cell membranes presumably cannot be explained by the Gi-Gs interaction, since the activity of the alpha subunit of Gs is not detectable in this variant. Several characteristics of Gi-mediated inhibition of adenylate cyclase have been studied in both S49 cyc- and wild type membranes. There are several similarities between inhibition of forskolin-stimulated adenylate cyclase by guanine nucleotides and somatostatin in cyc- and wild type membranes. 1) Somatostatin-induced inhibition of the enzyme is dependent on GTP; nonhydrolyzable GTP analogs are also effective inhibitors. 2) The effect of guanosine-5'-(3-O-thio)triphosphate (GTP gamma S) is essentially irreversible, and somatostatin accelerates GTP gamma S-induced inhibition. 3) Inhibition of adenylate cyclase by somatostatin or Gpp(NH)p is attenuated by treatment of cells with islet-activating protein (IAP). 4) Both cyc- and wild type membranes contain the substrate for IAP-catalyzed ADP-ribosylation (the alpha subunit of Gi). 5) beta Subunit activity in detergent extracts of membranes is liberated by exposure of the membranes to GTP gamma S. The alpha subunit of Gi in such extracts has a reduced ability to be ADP-ribosylated by IAP, which implies that this subunit is in the GTP gamma S-bound form. The resolved subunits of Gi have been tested as regulators of cyc- and wild type adenylate cyclase under a variety of conditions. The alpha subunit of Gi inhibits forskolin-stimulated adenylate cyclase activity in cyc-, while the beta subunit stimulates; these actions are opposite to those seen with wild type membranes. The inhibitory effects of GTP plus somatostatin (or GTP gamma S) and the alpha subunit of Gi are not additive in cyc- membranes. In wild type, the inhibitory effects of the hormone and GTP gamma S are not additive with those of the beta subunit.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Subunit dissociation and the inhibition of adenylate cyclase in S49 lymphoma cyc- and wild type membranes. 614 91


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