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)

We studied the different effects of three kinds of somatostatin (somatostatin 1-14, somatostatin 15-28, somatostatin 1-28) on the aggregation of rabbit's platelets. It was clarified that somatostatin 15-28 had inhibitory effects on rabbit's platelet aggregation stronger than somatostatin 1-14 did, and that somatostatin 1-28 did not have any such effects. These anti-aggregatory effects of somatostatin were stronger when induced by collagen than induced by ADP.
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PMID:Different effects of three kinds of somatostatin (15-28, 1-14, 1-28) on rabbit's platelet aggregation. 286 May 50

The neuropeptide somatostatin inhibits hormone release from GH4C1 pituitary cells via two mechanisms: inhibition of stimulated adenylate cyclase and a cAMP-independent process. To determine whether both mechanisms involve the guanyl nucleotide-binding protein Ni, we used pertussis toxin, which ADP-ribosylates Ni and thereby blocks its function. Pertussis toxin treatment of GH4C1 cells blocked somatostatin inhibition of both vasoactive intestinal peptide (VIP)-stimulated cAMP accumulation and prolactin secretion. In membranes prepared from toxin-treated cells, somatostatin inhibition of VIP-stimulated adenylate cyclase activity was reduced and 125I-Tyr1-somatostatin binding was decreased more than 95%. In contrast, pertussis toxin did not affect the biological actions or the membrane binding of thyrotropin-releasing hormone. These results indicate that ADP-ribosylated Ni cannot interact with occupied somatostatin receptors and that somatostatin inhibits VIP-stimulated adenylate cyclase via Ni. To investigate somatostatin's cAMP-independent mechanism, we used depolarizing concentrations of K+ to stimulate prolactin release without altering intracellular cAMP levels. Measurement of Quin-2 fluorescence showed that 11 mM K+ increased intracellular [Ca2+] within 5 s. Somatostatin caused an immediate, but transient, decrease in both basal and K+-elevated [Ca2+]. Consistent with these findings, somatostatin inhibited K+-stimulated prolactin release, also without affecting intracellular cAMP concentrations. Pertussis toxin blocked the somatostatin-induced reduction of [Ca2+]. Furthermore, the toxin antagonized somatostatin inhibition of K+-stimulated and VIP-stimulated secretion with the same potency (ED50 = 0.3 ng/ml). These results indicate that pertussis toxin acts at a common site to prevent somatostatin inhibition of both Ca2+- and cAMP-stimulated hormone release. Thus, Ni appears to be required for somatostatin to decrease both cAMP production and [Ca2+] and to inhibit the actions of secretagogues using either of these intracellular messengers.
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PMID:Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin. Evidence for coupling of Ni to decreases in intracellular free calcium. 286 57

Both forskolin, the activator of adenylate cyclase, and 8-bromocyclic (cAMP) increase cytosolic calcium levels (measured using Quin 2) and adrenocorticotropin (ACTH) release from a tumor cell line of the mouse anterior pituitary (AtT-20/D16-16). Somatostatin (SRIF) blocks the ACTH release response to each secretagogue but only inhibits forskolin-stimulated calcium mobilization suggesting that SRIF prevents the formation of cAMP rather than blocking the ability of cAMP to raise intracellular calcium concentrations. SRIF itself lowers intracellular calcium levels. The ACTH release response but not the rise in cytosolic calcium levels induced by the membrane-depolarizing agent K+, is blocked by SRIF, indicating that SRIF can interfere with some intracellular event, other than calcium mobilization or cAMP formation, to reduce ACTH secretion. Pertussis toxin uncouples SRIF receptors from adenylate cyclase by catalyzing the ADP-ribosylation of an inhibitory guanine nucleotide binding protein (Ni) in AtT-20 cell membranes. Pretreatment of AtT-20 cells with pertussis toxin abolishes the inhibition by SRIF of the ACTH release response and of the rise in cytosolic calcium induced by forskolin. In addition, the ability of SRIF to inhibit basal calcium levels is prevented by pertussis toxin treatment. Pertussis toxin treatment also reduced the ability of SRIF to inhibit K+-evoked ACTH release. SRIF receptor binding studies using the ligand 125I-CGP-23996 revealed that pertussis toxin treatment greatly diminished the affinity of the SRIF receptor for SRIF and its structural analogs. These results indicate that, in addition to coupling SRIF receptors to adenylate cyclase, Ni is also involved in the lowering by SRIF of resting calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin blocks somatostatin inhibition of calcium mobilization and reduces the affinity of somatostatin receptors for agonists. 286 3

It was shown that somatostatin (SRIF) inhibited cAMP-dependent vasoactive intestinal peptide (VIP)-stimulated prolactin (PRL) release by a GH3 clonal strain of rat pituitary tumor cells and decreased basal PRL secretion and inhibited PRL release in response to thyrotropin releasing hormone (TRH) whose action was independent of prior synthesis of cAMP. Pretreatment of these cells with pertussis toxin prevented SRIF's inhibitory effects on basal and TRH-stimulated hormone secretion as well as its VIP-stimulated responses. The blockade of SRIF's inhibitory effect on the actions of TRH or VIP was dependent on both the duration of preincubation and concentration of the toxin and was correlated with the ability of the toxin to catalyze the ADP-ribosylation of the 39,000-Da membrane protein. It is likely that this pertussis toxin substrate is involved in signal transduction of SRIF on cAMP-dependent actions of VIP and cAMP-independent action of TRH. However, the mechanism of SRIF's action on TRH is not clear, since SRIF did not affect the intracellular responses by TRH, neither intracellular Ca2+ mobilization nor the increase of 1,2-diacylglycerol formation following the breakdown of polyphosphoinositides.
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PMID:Pertussis toxin blocks the inhibitory effects of somatostatin on cAMP-dependent vasoactive intestinal peptide and cAMP-independent thyrotropin releasing hormone-stimulated prolactin secretion of GH3 cells. 286 31

The involvement of guanine nucleotide regulatory proteins in the steroidogenic response of the adrenal glomerulosa to angiotensin II (AII) was investigated by analyzing the effects of Bordetella pertussis toxin (PT) on several aspects of AII action. These included receptor binding, stimulation of aldosterone production and GTPase activity, inhibition of cAMP production, and attenuation of the aldosterone response at high angiotensin concentrations. Pretreatment of glomerulosa cells with PT abolished the inhibitory effects of both AII and somatostatin (SRIF) on ACTH-stimulated cAMP production. Under the same incubation conditions, the stimulation of aldosterone secretion by submaximal and maximal steroidogenic concentrations of AII was completely unaffected by the toxin. However, the attenuation of steroid responses seen with supramaximal concentrations of AII was abolished. In addition, the ability of SRIF to inhibit AII-stimulated steroid production was markedly reduced by PT treatment. The binding of [125I]AII to high affinity sites in intact cells and particulate fractions, and modulation of the binding by guanine nucleotides, were unaffected by toxin pretreatment, even under conditions where a 40-41K protein was completely ADP ribosylated. In contrast, the toxin substantially diminished the binding of [125I]Tyr0-SRIF to SRIF receptors in glomerulosa cells (by 50% after 5 h and by 90% after 20 h). These results indicate that Ni or a similar protein probably mediates the inhibition of cAMP formation by AII and the attenuation of the steroid response by high concentrations of AII as well as the inhibitory actions of SRIF in the adrenal glomerulosa cell. Furthermore, the lack of effect of PT on AII binding and stimulation of GTPase activity suggests the existence of an additional pertussis-insensitive guanine nucleotide-regulatory protein that is activated by lower concentrations of AII and mediates the stimulation of aldosterone production.
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PMID:Control of aldosterone production by angiotensin II is mediated by two guanine nucleotide regulatory proteins. 288 77

Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (Ni) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125I-[Tyr1]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p] greater than GTP greater than GDP greater than GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+. When pancreatic acini were treated with 1 microgram/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin binding to acinar membranes was reduced. Gpp(NH)p further decreased somatostatin binding to islet-activating protein (IAP)-treated acinar membranes. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. Furthermore, exposure of acini to IAP caused ADP ribosylation of a membrane protein with Mr = 41,000 in parallel to the inhibition of cAMP accumulation in acini. The present results suggest, therefore, that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor.
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PMID:Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes. 288 15

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

The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog [125I]CGP 23996. [125I]CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was to a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity [125I]CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of [125I]CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect [125I]CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with [125I] CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to [125I]CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin modifies the characteristics of both the inhibitory GTP binding proteins and the somatostatin receptor in anterior pituitary tumor cells. 290 Mar 31

The molecular mechanisms of somatostatin (SRIF) desensitization were investigated in the anterior pituitary tumor cell line AtT-20. Previous studies have shown that pretreatment of AtT-20 cells with SRIF analogs desensitizes the cells to SRIF inhibition of hormone release, cyclic AMP formation and calcium influx. This desensitization may involve a change in the properties of the SRIF receptors. Pretreatment of AtT-20 cells with Trp8-SRIF reduced the binding of the SRIF analog [125I]CGP 23996 (des-Alal, Gly2-[desamino-Cys3, Tyr11]-3, 14-dicarbasomatostatin) to AtT-20 cell membranes. The loss of [125I]CGP 23996 binding was dependent on the time of Trp8-SRIF treatment and was reversible. The ability of GTP analogs to inhibit [125I]CGP 23996 binding was reduced after Trp8-SRIF treatment, suggesting that the SRIF receptor and the inhibitory G proteins become uncoupled during desensitization. This is indicated further by the decrease in SRIF stimulation of GTPase activity and SRIF inhibition of forskolin-stimulated adenylyl cyclase activity in desensitized membranes. The reduction and recovery of SRIF inhibition of adenylyl cyclase activity after Trp8-SRIF pretreatment has a similar time course as the changes in [125I]CGP 23996 binding. GTP inhibition of forskolin-stimulated adenylyl cyclase activity is also reduced in SRIF-desensitized membranes. The loss of the GTP effect occurs rapidly and does not fully recover after Trp8-SRIF pretreatment. The levels of ADP-ribosylation of inhibitory GTP binding protein, the relative quantity of the alpha subunits of the inhibitory G proteins and their electrophoretic mobility after 2-dimensional gel electrophoretic analysis, are not altered in SRIF-desensitized membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristics of somatostatin desensitization in the pituitary tumor cell line AtT-20. 290 14

Development of an enriched cultured cell system allowed us to investigate the mechanism of cholinergic inhibition of somatostatin release stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+-protein kinase C-dependent pathways of cell activation. After a 24-h culture on rat tail collagen, D-cells, quantified by immunohistochemistry, were 18-fold enriched compared with unelutriated dispersed cells. Somatostatin release from cultured cells was expressed as a percent of the somatostatin released by a specific stimulus in control cells. Under basal conditions release of somatostatin was 2.3 +/- 0.6% of the total cell content. Epinephrine (1 microM) and cholecystokinin octapeptide (10 nM) increased somatostatin release to 6.98 +/- 1.25 and 10.72 +/- 1.64%, respectively. Carbachol (1 microM) completely inhibited somatostatin release stimulated by epinephrine and reduced cholecystokinin octapeptide-stimulated release to 75% of control levels. Carbachol inhibition of the response to both epinephrine and cholecystokinin octapeptide was totally prevented by 5 h of treatment of the cells with pertussis toxin (300 ng/ml). Somatostatin release in response to the diterpene forskolin (10 microM), dibutyryl cAMP (300 microM), the phorbol ester beta-phorbol 12-myristate 13-acetate (0.1 microM), and the calcium ionophore A23187 (1 microM) was also inhibited by carbachol and prevented by pertussis toxin pretreatment. The ADP-ribosylase inhibitor isonicotinamide (1 mM) selectively blocked the effect of pertussis toxin without altering other stimulatory or inhibitory responses. These data are consistent with the view that carbachol inhibits somatostatin release at guanyl nucleotide-binding protein and/or another pertussis toxin-sensitive site.
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PMID:Pertussis toxin-sensitive cholinergic inhibition of somatostatin release from canine D-cells. 290 2


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