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)

Short-lasting hypothermia during thiobutabarbital general anaesthesia causes no decrease of the absolute ATP level in the blood and liver of rats. The adenylate energy charge in the tissues is relatively high - 0.86 in the liver and 0.85 in the muscles, which might be an evidence of a significant "energy sparing" during moderate hypothermia (26 +/- 1 degree C). Somatostatin in a dose of 20 micrograms/kg of body weight given to the rats during hypothermia decreased the ATP level, the ATP/ADP ratio and the adenylate energy charge in the studied tissues, especially in the liver, evidencing increased intensity of catabolic processes caused by the inhibitory action of somatostatin on the release of insulin and glucagon, among other hormones, and on the change of the insulin/glucagon ratio.
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PMID:Somatostatin effect on the level of adenyl nucleotides in the blood and tissues of rats during short-lasting hypothermia. 614 95

The mechanism underlying the positive inotropic and chronotropic effects of capsaicin were investigated using the spontaneously beating guinea-pig atrium in vitro. Capsaicin induced a long-lasting stimulatory effect (threshold dose 10(-9) M). Tetrodotoxin, phentolamine, 6-OHDA, mepyramine plus cimetidine, methysergide-, indomethacin-, somatostatin- or morphine pretreatment and local treatment with capsaicin on the vagal nerves did not reduce the capsaicin response, while it was abolished up to 1 month after systemic capsaicin pretreatment. The capsaicin response was subject to a rapid tachyphylaxis. During capsaicin tachyphylaxis, the positive inotropic and chronotropic effects of noradrenaline, serotonin and histamine were unchanged. Various neuropeptides were investigated with regard to cardiac activity. Physalaemin, eledoisin and somatostatin had negative inotropic and chronotropic effects. Substance P, bombesin, kassinin, CCK-8 or PHI (up to 10(-6)M of each) did not cause any detectable response on the guinea-pig auricle, while the substance P antagonist [D-Arg, D-Pro, D-Trp, Leu]SP induced a long-lasting stimulation of heart activity, VIP also stimulated the heart. Various adenyl compounds were also tested. Adenosine, AMP, ADP, ATP and beta-, gamma-methylene ATP had negative chronotropic and inotropic effects, while alpha-, beta-methylene ATP induced a stimulatory response. During alpha-, beta-methylene ATP tachyphylaxis, the auricles still responded to capsaicin. The inhibitory effects of adenosine and ATP analogues were antagonized by theophylline and 8-p-sulfophenyl theophylline. Capsaicin induced a small release of labelled nucleotides from 3(H)-adenine-prelabelled atria from control, but not from capsaicin-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Capsaicin-induced stimulation of the guinea-pig atrium. Involvement of a novel sensory transmitter or a direct action on myocytes? 620 51

alpha 2-Adrenoceptor agonists and somatostatin (SS) exert opposite effects on the spike discharge of pyramidal and granule cells in the rat hippocampus. We studied whether clonidine, an alpha 2-adrenoceptor agonist, and yohimbine, an alpha 2-adrenoceptor antagonist, can modulate somatostatin-like immunoreactivity (SSLI) levels, binding of 125I-Tyr11-somatostatin (125I-Tyr11-SS) to its specific receptors, SS-inhibited adenylyl cyclase (AC) activity, and the guanine-nucleotide binding regulatory proteins Gi and G(o) in the rat hippocampus. Clonidine (1 mg/kg, intraperitoneally (IP) or yohimbine (5 mg/kg, IP) injected at both 10 and 16 hours before decapitation did not affect SSLI content in the hippocampus. Clonidine administration decreased the number of specific SS receptors and increased the apparent affinity in hippocampal membranes. This change in SS binding was not the result of a direct effect of clonidine on these receptors because no effect in binding was produced by high concentrations of clonidine (10(-5) M) when added in vitro. Pretreatment with yohimbine prevented the clonidine-induced in SS binding. Yohimbine alone produced a significant increase in the number of 125I-Tyr11-SS receptors and a decrease in its apparent affinity. Clonidine decreased the ADP-ribosylation of a 41- and a 39-kDa G-protein by pertussis toxin (PTX), whereas yohimbine had no effect on the PTX-catalyzed ADP-ribosylation. No significant differences were seen for the basal or for the forskolin (FK)-stimulated AC enzyme activities in the control, clonidine- and/or yohimbine-treated groups. Somatostatin caused a significantly lower inhibition in AC activity in hippocampal membranes of clonidine-treated rats, whereas yohimbine led to an opposite effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-2 adrenoceptors modulate the somatostatinergic system and G protein levels in the rat hippocampus. 776 86

Adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a P2y purinergic agonist, has been shown to be a potent insulin secretagogue on the isolated rat pancreas. In the present work the effects of ADP beta S on insulin somatostatin, and glucagon secretions were investigated in dogs. In vivo, in anesthetized fasted dogs, i.v. ADP beta S (0.1 mg kg-1) induced an immediate increase in insulin and somatostatin-like immunoreactivity (SLI) but not in glucagon pancreaticoduodenal outputs. In conscious fasted dogs, i.v. ADP beta S (0.1 mg kg-1) produced an immediate and transient augmentation in plasma insulin levels but not in plasma SLI and glucagon levels. In vitro, the effects of ADP beta S were investigated on the isolated uncinate process of dog pancreas, from normal and alloxan-diabetic animals. In normal uncinate process, in presence of 8.3 mM glucose, ADP beta S (1 microM) stimulated insulin and SLI releases but not glucagon release. On uncinate process from diabetic animals, ADP beta S (1 microM) retained its stimulating effects but the responses were impaired as compared with normal dogs: Insulin response was drastically diminished and SLI response strongly enhanced. In conclusion, ADP beta S is a potent insulin secretory agent in dog. This P2y purinoceptor agonist, which exerts a direct stimulatory effect on pancreatic SLI, is interestingly devoid of direct glucagonotropic properties.
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PMID:In vivo and in vitro effects of adenosine-5'-O-(2-thiodiphosphate) on pancreatic hormones in dogs. 780 20

The present study investigates the effects of the administration of an intracerebroventricular (i.c.v.) dose of 500 micrograms/rat of the neuroleptic (-) sulpiride on somatostatin-like immunoreactivity (SSLI) levels, 125I-Tyr11-SS binding to its specific receptors, SS-modulated adenylyl cyclase (AC) activity and the pertussis toxin (PTX) substrates measured by toxin-catalysed ADP ribosylation of the alpha-subunits from G-proteins. (-) Sulpiride significantly decreased the SSLI levels in the frontoparietal cortex at 30 min but was without effect on the SSLI concentration in the striatum. This decrease had disappeared within 24 hr. The administration of (-) sulpiride produced a significant increase in the number of 125I-Tyr11-SS receptors and a significant reduction in their affinity at 30 min after injection in the striatum without affecting the frontoparietal cortex. The effects of the (-) sulpiride injection had disappeared after 24 hr. This change in SS binding was not due to a direct effect of (-) sulpiride on these receptors since no effect on binding was produced by high concentrations of (-) sulpiride (10(-5) M) when added in vitro. No significant differences were seen in either brain region for the basal or the forskolin (FK)-stimulated AC enzyme activities in the control and (-) sulpiride groups. In the (-) sulpiride group, the capacity of SS to inhibit FK-stimulated AC in the frontoparietal cortex was significantly higher than in the control group with no significant difference in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of sulpiride on somatostatin receptors, somatostatin-like immunoreactivity and modulation of adenylyl cyclase activity in the rat brain. 793 12

Incubation of GH4C1 rat pituitary cell membranes with the poorly hydrolyzable GTP analogue, GTP gamma S, produces a decrease in the pertussis toxin-catalyzed ADP-ribosylation of 40-kDa protein in the membrane pellet and the release of an alpha-like substrate from the membrane into the supernatant fraction; these effects do not occur with the inactive GDP analogue, GDP beta S. The resolved supernatant fraction from GTP gamma S-stimulated membranes is significantly activated to pertussis toxin-catalyzed [32P]ADP-ribosylation by the addition of purified beta gamma complex. Immunoblot analysis identifies the released pertussis toxin substrate as alpha subunits of Gi2, Gi3, and G(o) in the resolved supernatant. The physiological agonist, somatostatin, also stimulates the release of Gi2 and G(o) alpha subunits but not Gi3 from GH4C1 cell membranes in the presence of a low concentration of GTP gamma S (20 nM). The effects of somatostatin are inhibited by pretreatment of GH4C1 cells with pertussis toxin. Furthermore, the addition of somatostatin to intact GH4C1 cells decreases the level of Gi2 alpha subunits in the crude membrane whereas immunoblot analysis of the 274,000 x g supernatant (cytosolic fraction) clearly shows the presence of Gi2 alpha subunits. These data indicate that pertussis toxin-sensitive G proteins in GH4C1 cells dissociate into alpha subunits and beta gamma complex with the release of the alpha subunits from the membranes upon somatostatin activation.
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PMID:Somatostatin induces release of the alpha subunits of pertussis toxin-sensitive G proteins in native membranes and in intact GH4C1 rat pituitary cells. 810 May 41

Using the functionally differentiated colonic cell line, HT29-19A, we have examined sites at which inhibitory G-proteins mediate the antisecretory actions of somatostatin (SST) and the alpha 2-adrenergic agonist, clonidine (CLON) at the epithelial level. Both agents caused a dose-dependent inhibition (EC50:SST 35 nM; CLON 225 nM) of Cl- secretion (assessed by changes in short circuit current) activated by cAMP-mediated agonists, PGE2 and cholera toxin. Inhibition was accompanied by a reduction in intracellular cAMP accumulation and could be blocked by pretreatment with pertussis toxin at a concentration (200 ng/ml) which activated ADP-ribosylation of a 41-kD inhibitory G protein in HT29-19A membranes. Secretion stimulated by the permeant cAMP analogue, dibutyryl cAMP, was also inhibited by SST and CLON (30-50%; P < 0.005), indicating additional inhibitory sites located distal to cAMP production. Both agents were effective inhibitors of secretion mediated through the Ca2+ signaling pathway. SST (1 microM) and CLON (10 microM) reduced the Isc response to the muscarinic agonist, carbachol, by 60-70%; inhibition was reversed in pertussis toxin-treated cells. These effects did not, however, involve inhibition of the carbachol-induced increase in cellular inositol 1,4,5-trisphosphate levels or the rise in cytosolic calcium, [Ca]i. Inhibition by SST of secretion induced by phorbol 12,13 dibutyrate but not by the calcium agonist, thapsigargin, suggests that SST may act at a distal inhibitory site in the Ca(2+)-dependent secretory process activated by protein kinase C. We conclude that SST and alpha 2-adrenergic agonists can act directly on intestinal epithelial cells to exert a comprehensive inhibition of Cl- secretion mediated through both cAMP and Ca2+/protein kinase C signaling pathways. Inhibition is mediated via pertussis toxin-sensitive G-proteins at sites located both proximal and distal to the production of second messengers.
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PMID:Multiple G-protein-dependent pathways mediate the antisecretory effects of somatostatin and clonidine in the HT29-19A colonic cell line. 810 78

Somatostatin (SS) and noradrenaline (NA) are distributed in the rat cerebral cortex, and seizure activity is one of the aspects of behavior affected by both neurotransmitters. Due to the possible interaction between both neurotransmitter systems, we studied whether phenylphrine, an alpha 1-adrenoceptor agonist, and prazosin, an alpha 1-adrenoceptor antagonist, can modulate SS-like immunoreactivity (SS-LI) levels, binding of [125I][Tyr11]SS to its specific receptors, the ability of SS to inhibit adenylate cyclase (AC) activity, and the guanine nucleotide binding regulatory protein G, and G., in the Sprague-Dawley rat frontoparietal cortex. An IP dose of 2 or 4 mg/kg of phenylephrine injected 7 h before decapitation decreased the number of SS receptors and increased the apparent affinity in frontoparietal cortex membranes. An IP dose of 20 or 25 mg/kg of prazosin administered 8 h before decapitation increased the number of SS receptors and decreased their apparent affinity. The administration of prazosin before the phenylephrine injection prevented the phenylephrine-induced changes in SS binding. The addition of phenylephrine and/or prazosin 10(-5) M to the incubation medium changed neither the number nor the affinity of the SS receptors in the frontoparietal cortex membranes. Phenylephrine or prazosin affected neither SS-LI content nor the basal or forskolin (FK)-stimulated AC activities in the frontoparietal cortex. In addition, SS caused an equal inhibition of AC activity in frontoparietal cortex membranes of phenylephrine-and prazosintreated rats compared with the respective control group. Finally, phenylephrine and prazosin did not vary the pertussis toxin (PTX)-catalyzed ADP ribosylation of Gi- and/or Go-proteins. These results suggest that the above-mentioned changes are related to the phenylephrine activation of alpha 1-adrenoceptors or to the blocking of these receptors by prazosin. In addition, these data provide further support for a functional interrelationship between the alpha 1-adrenergic and somatostatinergic systems in the rat frontoparietal cortex.
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PMID:Effect of phenylephrine and prazosin on the somatostatinergic system in the rat frontoparietal cortex. 874 58

Interleukin 6 is a pleiotropic cytokine produced in the central nervous system (CNS) that has been involved in both direct neurotrophic activities and in the regulation of the production of acute phase proteins both at peripheral and central levels. In rat cortical type I astrocytes, interleukin 6 release is under the control of cAMP-protein kinase A and calcium-phospholipids-protein kinase C systems. Somatostatin is a neuropeptide, acting as a neurotransmitter, highly concentrated within the CNS, where it has been involved in the modulation of learning and memory processes. The aim of this study was to characterize the effects of somatostatin on the release of interleukin 6 from rat cortical type I astrocytes and the intracellular mechanisms involved in this activity. Our results show that somatostatin, in a concentration-dependent manner, inhibited basal and forskolin-stimulated interleukin 6 release from rat cortical type I astrocytes in culture. The EC50 of the inhibitory action was calculated to be approximately 10 nM. Furthermore, this effect of somatostatin was completely abolished by pretreating cortical astrocytes with pertussis toxin that, uncoupling, by ADP-rybosylating, the inhibitory GTP-binding protein from the receptors, prevents the activation of the intracellular effectors such as the adenylyl cyclase enzyme. To identify the intracellular mechanism mediating the effects of somatostatin on the interleukin 6 release, we evaluated the peptide modulation of basal and stimulated intracellular accumulation of cAMP. In our experimental conditions somatostatin significantly inhibited both basal and forskolin-stimulated cAMP accumulation. Conversely, somatostatin did not affect the increase of interleukin 6 release induced by dibutyryl-cAMP, a nonhydrolizable cAMP analog that, bypassing the effects of somatostatin on adenylyl cyclase activity, directly activated protein kinase A. These observations support the hypothesis that somatostatin inhibitory activity on interleukin 6 release is mediated by its effects on cAMP production. Somatostatin analog SMS 201-995 did not affect interleukin 6 production either in basal or stimulated conditions. Since, SMS 201-995 was reported to bind with high affinity only to somatostatin receptors type 2, 3 and 5, the lack of effect of this compound on interleukin 6 release suggests that the inhibitory action of somatostatin could be mediated by the activation of either type 1 or type 4 somatostatin receptors. In conclusion, our data demonstrate that the release of interleukin 6 from rat cortical type I astrocytes is inhibited by somatostatin through the activation of a somatostatin receptor coupled to the inhibition of adenylyl cyclase via a G-protein sensitive to pertussis toxin.
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PMID:Somatostatin inhibits interleukin 6 release from rat cortical type I astrocytes via the inhibition of adenylyl cyclase. 919 70

The delta-cell line RIN14B was characterized with regard to ATP-regulated K+ (K(ATP)) channel activity and hormone release. By applying the patch-clamp technique, dose-response curves for ATP and the sulfonylurea tolbutamide were obtained in inside-out patches. The concentration causing half-maximal K(ATP) channel inhibition was found to be 23.7 and 27.6 microM for ATP and tolbutamide, respectively. ADP and diazoxide stimulated K(ATP) channel activity, an effect dependent on the presence of intracellular Mg2+. The stimulatory effect of diazoxide also required the presence of ATP. The kinetic properties of the K(ATP) channel were analysed in the presence of ATP, a combination of ADP and ATP and in nucleotide-free solutions. The distribution of K(ATP) channel open time could be described by a single exponential function with a time constant of approximately 30 ms in nucleotide-free and in ATP-containing solutions. The presence of both ATP and ADP resulted in the appearance of an additional time constant of > 150 ms. Single-channel unitary current-voltage (i-V) relation was characterised for the K((ATP) channel present in RIN14B cells. The slope conductance, measured at the reversal potential was found to be 19.1 +/- 2.4 pS. The permeability for K+ ions was calculated to be 0.31 x 10(-13) cm3 x s(-1). We have not been able to confirm the somatostatin releasing profile of the RIN14B cells using radioimmunoassays, nor could we find positive somatostatin stain with immunocytochemical techniques. We conclude that the RIN14B cell line, previously characterized as a somatostatin-secreting cell line, contains K(ATP) channels with properties closely resembling the K(ATP) channel described in the pancreatic beta-cell. However, the cell line appears to have dedifferentiated with regard to the ability to secrete somatostatin, maintaining the highly differentiated function of both insulin biosynthesis and exocytosis.
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PMID:RIN14B: a pancreatic delta-cell line that maintains functional ATP-dependent K+ channels and capability to secrete insulin under conditions where it no longer secretes somatostatin. 927 Dec 25

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