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)

The influence of human and rat recombinant interleukin-1 (hIL-1 beta and -1 alpha and rIL-1 beta) on acid secretion was investigated in conscious pylorus-ligated rats. Intravenous injection of either hIL-1 beta, hIL-1 alpha or rIL-1 beta dose dependently inhibited gastric acid output with an ED50 of 0.05 microgram, 0.5 microgram and 2.2 micrograms, respectively. The antisecretory action of IL-1 beta was associated with an increase in circulating levels of gastrin. hIL-1 beta-induced inhibition of acid secretion was dose dependently reversed by peripheral injection of the IL-1 receptor antagonist, IL-RA, with a dose ratio of 1:10(3) for complete reversal. The inhibitory effect of hIL-1 beta was blocked by indomethacin and was not modified by IV injections of the CRF receptor antagonist, alpha-helical CRF(9-41), or the monoclonal somatostatin antibody CURE.S6, or by systemic capsaicin pretreatment. These results show that systemic hIL-1 beta-induced inhibition of gastric acid secretion is mediated through IL-1 receptors and prostaglandin pathways, and does not involves CRF receptors, afferent fibers, or changes in circulating gastrin or somatostatin levels.
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PMID:Potent inhibition of gastric acid secretion by intravenous interleukin-1 beta and -1 alpha in rats. 140 1

Previous work had shown that interleukin 1 (IL-1), after a long period of treatment, stimulates beta-endorphin release and potentiates the effects of secretagogues in AtT-20 cells, a mouse anterior pituitary cell line. Treatment of AtT-20 cells with IL-1 induced a transient and early stimulation of mRNA expression by both immediate-early protooncogenes Fos and Jun (mouse c-fos and c-jun). The effect appeared within 30 min, and returned to basal levels after 2 hr. Desensitization of protein kinase C by phorbol ester pretreatment had no effect on the ability of IL-1 to induce Fos and Jun mRNA expression. Somatostatin, an inhibitor of cAMP and beta-endorphin secretion, did not reduce the IL-1 effect on Fos and Jun mRNA expression. Addition to AtT-20 cells of antisense oligonucleotides to Fos and Jun abolished the secretion induced by IL-1. These results indicate that immediate-early signals Fos and Jun are involved in IL-1-induced beta-endorphin secretion in AtT-20 cells.
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PMID:Interleukin 1 induces beta-endorphin secretion via Fos and Jun in AtT-20 pituitary cells. 197 16

Cytokine effects on permanent cell lines of transformed mouse pancreatic alpha- and beta-cells were compared. The beta-tumor cell 1 (beta TC1) line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat insulin II promoter) produced insulin predominantly, although small quantities of intracellular glucagon (100:1 insulin to glucagon) were detectable by radioimmunoassay. The alpha TC1 line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat preproglucagon promoter) produced not only glucagon but also considerable quantities of insulin (4:1 glucagon to insulin) and preproinsulin mRNA. We therefore cloned alpha TC1 cells and obtained 12 glucagon-producing clonal cell lines that did not produce levels of insulin detectable by radioimmunoassay. Analysis by Northern blotting of total RNA from two lines, alpha TC1 clones 6 and 9, confirmed the absence of preproinsulin mRNA. No somatostatin or pancreatic polypeptide was detected by immunohistochemical staining in alpha TC1 clones 6 or 9 or beta TC1 cells. Rat recombinant gamma-interferon (IFN-gamma; 5-250 U/ml) or mouse recombinant interleukin 1 (IL-1; 1-25 U/ml) individually inhibited DNA synthesis in beta TC1 cells after 3 days of treatment. The two cytokines in combination acted synergistically to further depress DNA synthesis and increase cytotoxicity. In contrast, alpha TC1 clone 9 cells were not sensitive to inhibition of DNA synthesis by each cytokine individually, although glucagon synthesis was inhibited. The combination of these cytokines caused marked inhibition of DNA and glucagon syntheses in alpha TC1 clone 9 cells. alpha TC1 clone 9 cells were somewhat more resistant to the cytotoxic action of the combined cytokines than were beta TC1 cells. Incubation with 50 U/ml IFN-gamma induced class II MHC molecules (I-Ab, I-Ad, and I-Ed) and enhanced the constitutive expression of class I molecules (H-2Kb and H-2Kd) on the cell surfaces of beta TC1, uncloned alpha TC1, and alpha TC1 clones 6 and 9. Thus, these cell lines are heterozygous for MHC alleles derived from both parental strains used in the construction of the transgenic mice [C57BL/6J (H-2b) and DBA/2J (H-2d)]. Class II gene transcription induced by IFN-gamma was confirmed in beta TC1 and alpha TC1 clone 9 cells by Northern blot analysis with A alpha-, A beta-, E alpha, and E beta-DNA probes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of cytokine effects on mouse pancreatic alpha-cell and beta-cell lines. Viability, secretory function, and MHC antigen expression. 210 69

It has long been known that endogenous pyrogen, released as a result of injection of typhoid vaccine or in response to infection, produces fever and increases ACTH secretion. Recent studies have indicated that endogenous pyrogen is, at least in part, IL-1. This monokine has now been shown to activate the release of ACTH by a hypothalamic mechanism with release of CRF and possibly vasopressin, which stimulates the corticotrophs. There may also be a pituitary action to stimulate the release of ACTH directly. In our experiments we showed that IL-1 at low but not higher doses appears to act intrahypothalamically to stimulate GH and PRL release and to inhibit TSH release. In the meantime, another monokine, cachectin, was isolated and its structure determined. We have found that this monokine can act following its third ventricular injection to stimulate ACTH, PRL, and GH release and to inhibit TSH release, at least in part, by release of prostaglandins since indomethacin, an inhibitor of prostaglandin synthesis, produced a blockade of the responses except for those of ACTH. This peptide also has highly potent effects to alter pituitary hormone release by direct action on the pituitary to stimulate ACTH, GH, and TSH and to a slight extent PRL release. These actions appear to involve prostaglandins since indomethacin blocks all of the effects except for the effect on ACTH secretion. This monokine also produces a dose-related lowering of anterior pituitary cyclic AMP levels. When the monokine was incubated along with somatostatin, the lowering of cyclic AMP was reversed, and a potent PRL-releasing effect of the monokine was visible. We have begun studies with a third monokine, gamma interferon, which indicate that it stimulates ACTH release but suppresses plasma GH and TSH levels by a hypothalamic action. It is apparent that these various monokines have powerful effects to alter hypothalamic-pituitary function and that they probably mediate most of the effects of infections on the release of anterior pituitary hormones.
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PMID:Role of monokines in control of anterior pituitary hormone release. 223 30

This study extends the neuroendocrine role of central interleukin-1 beta (IL-1 beta) during the stress of lipopolysaccharide (LPS) challenge to include inhibition of the somatotropic [GH-releasing hormone (GHRH)-somatostatin (SRIF)-GH] axis in juvenile male rats and clarifies the role of CRF in the mediation of LPS/IL-1-induced changes in GHRH and SRIF neurosecretion. The results of the in vivo component of this study demonstrated that LPS treatment (2.5 mg/kg twice daily for 5 days) caused a significant attenuation of body weight gain for 2 days (2.4 +/- 1.7% vs. 10.3 +/- 1.8% BW/day in saline controls; P < 0.05) and failure of catch-up growth thereafter even though a small transient suppression of food intake returned to normal by the second of 4 days of treatment. Associated with the first day of growth attenuation was an acute suppression of all plasma GH parameters, including GH mass (area under the curve, 1.972 +/- 0.1837 vs. 6.402 +/- 1.7 micrograms/ml.6 h for saline controls; P < 0.05), in animals receiving an acute bolus of LPS, which was blocked by prior microinjection of IL receptor antagonist protein (IRAP) into the third ventricle. In contrast, GH parameters associated with the second day of LPS-suppressed body weight gain were increased (GH mass, 9.4 +/- 2.2 vs. 3.5 +/- 0.5 micrograms/ml.4 h in saline controls; P < 0.05). These increases were reversed after another 2 days of LPS treatment. In a series of in vitro experiments using medial basal hypothalamic (MBH) explants incubated with LPS [100 ng/ml alone or with 10(-7) M IRAP or 10(-6) M CRF antagonist (CRF-ANT)], GHRH release from MBH incubated with LPS was significantly greater than that in controls (231 +/- 79% vs. 71 +/- 34% of baseline release; P < 0.05), and this stimulation was antagonized by both IRAP and CRF-ANT. SRIF release was significantly increased by incubation with LPS (163 +/- 28% vs. 97 +/- 20% of the baseline for controls; P < 0.05) and blocked (to 88 +/- 14% of the baseline) by IRAP, but not by CRF-ANT. Finally, when MBH explants were incubated with IL-1 beta (10(-9) M), there was a significant inhibition of in vitro GHRH release (37.9 +/- 6.7% vs. 74.9 +/- 16.6% for controls), which was reversed by IRAP and CRF-ANT, and a significant stimulation of SRIF release (168.7 +/- 37.5% vs. 98.0 +/- 11.6% for controls), which was reversed by IRAP, but not CRF-ANT.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endotoxin-induced suppression of the somatotropic axis is mediated by interleukin-1 beta and corticotropin-releasing factor in the juvenile rat. 762 73

Intracerebroventricular (ICV) injection of interleukin (IL)-1 alpha has previously been demonstrated to enhance the rate of whole body glucose disposal. The purpose of the present study was to identify the specific tissue(s) responsible for the increased glucose uptake. All experiments were performed on fasted catheterized rats in which an ICV cannula had also been implanted. In vivo glucose uptake by individual tissues was determined, using tracer amounts of [14C]-2-deoxyglucose, 20-60 min after the ICV injection of recombinant human IL-1 alpha (100 ng/rat). IL-1 increased glucose uptake in skeletal muscle (117%), diaphragm (50%) and heart (110%), compared to time-matched control animals. Glucose uptake by other tissues, including the liver, spleen, lung, skin, ileum and whole brain, was not different from control values. As a result of these changes, the contribution of skeletal muscle to whole body glucose disposal increased from 29% to 48%, while that of skin and intestine decreased. The increased glucose uptake in various muscles was consistent with the increased (55%) plasma insulin levels in these animals. In rats pretreated with somatostatin, which produced severe insulinopenia, the IL-1 induced increases in glucose uptake were prevented in heart and diaphragm, and attenuated by more than 80% in skeletal muscle. These data indicate that the increased whole body glucose disposal produced by ICV injection of IL-1 alpha was due to an enhanced uptake of glucose by muscle via insulin-mediated pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Central administration of IL-1 alpha increases glucose uptake by muscle. 774 67

It is well established that IL-1 beta acts in the brain to potently inhibit gastric acid secretion in pylorus-ligated rats. The present study was designed to further investigate the specificity and mechanisms of the centrally mediated antisecretory action of IL-1 beta in conscious rats. Intracerebroventricular injection of IL-1 beta (100 ng) decreased acid secretion in pylorus-ligated rats and inhibited basal and pentagastrin-stimulated acid secretion in rats with chronic gastric fistula. The antisecretory effect of IL-1 beta (100 ng) injected into the lateral ventricle of pylorus ligated rats was completely reversed by prior intracerebroventricular injection of the IL-1 receptor antagonist, IL-1ra, (100 micrograms). Peripheral administration of the somatostatin monoclonal antibody, CURE.S6, did not modify intracisternal IL-1 beta-induced inhibition of acid secretion in pylorus ligated rats. IL-6 and tumor necrosis factor-alpha (100 ng) injected intracisternally did not influence gastric acid secretion in pylorus-ligated rats. These data show that IL-1 beta action in the CNS is mediated through interaction with specific IL-1 receptors and is selective to this cytokine. IL-1 beta antisecretory action can be observed under basal and pentagastrin-stimulated conditions and is independent from somatostatin release in the periphery.
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PMID:Central interleukin-1 beta-induced inhibition of acid secretion in rats: specificity of action. 843 8

In the present study, we examined the in vitro and in vivo modulation of IL-1 receptors by stress and endotoxin treatment. The treatment of AtT-20 mouse pituitary adenoma cells for 24 h with neuroendocrine mediators of stress such as CRF and catecholamines produced dose-dependent increases in cAMP production and [125I]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increases in [125I]IL-1 alpha binding. Furthermore, in keeping with the effects of stress mediators to up-regulate IL-1 receptors in AtT-20 cells, ether-laparotomy stress in mice resulted in a significant increase in [125I]IL-1 alpha binding in the pituitary with no significant alterations observed in the brain; in contrast, [125I]oCRF binding in the pituitary was significantly decreased after the ether-laparotomy stress. Next, we investigated the modulation of IL-1 beta levels and [125I]IL-1 alpha binding following endotoxin treatment. IL-1 beta levels were dramatically increased in the peripheral tissues (pituitary, testis, and spleen) at 2-6 h after a single LPS injection (30 micrograms LPS/mouse); however, no significant changes were observed in brain (hippocampus and hypothalamus). [125I]IL-1 alpha binding in the pituitary gland, liver, spleen, and testis was significantly decreased at 2 h following a single administration of both low (30 micrograms LPS/mouse) and high (300 micrograms LPS/mouse) doses of endotoxin. [125I]IL-1 alpha binding in the hippocampus was not significantly altered at 2 h by low dose of LPS and was significantly decreased by high-dose administration of LPS (300 micrograms/mouse). Following two LPS injections (at 0 and 12 h), dramatic increases in IL-1 beta concentrations in the hypothalamus, hippocampus, spleen, and testis were observed at 2 h after the second LPS injection; a small but statistically nonsignificant change was evident in the pituitary. Moreover, dramatic decreases in [125I]IL-1 alpha binding were seen after two injections of 30 micrograms LPS/mouse in both central and peripheral tissues. These data provide further support for a role for IL-1 in coordinating brain-endocrine-immune responses to stress and infection.
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PMID:Interleukin-1 receptors in the brain-endocrine-immune axis. Modulation by stress and infection. 859 15

Somatostatin and other neuropeptides are known to modulate the proliferative capacity of immune cells. In the present study, we investigated the expression of Somatostatin receptor (SSTR) subtypes on rat thymocytes. RT-PCR analysis of fresh thymocytes showed significant levels of transcripts for the SSTR2 whereas transcripts for the SSTR1 and SSTR3 were not detectable. Interestingly, when the thymocytes were activated with low concentration of Phytohemagglutinin and interleukin 1, the transcript for SSTR1 was markedly increased. Lymphokine induced activation of thymocytes selectively upregulated the SSTR1 since, transcripts for SSTR2 remained the same after activation and SSTR3 was not detectable. PCR amplified fragment of SSTR1 from the activated thymocytes showed identical sequence to the rat brain receptor. The physiological significance of the increase of SSTR1 mRNA in thymocytes after activation remains to be elucidated but it may be possible that these two different subsets of receptors (SSTR1 and SSTR2) are involved in the modulation of thymocyte proliferation and differentiation.
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PMID:Activation of rat thymocytes selectively upregulates the expression of somatostatin receptor subtype-1. 893 24

It is now largely established that the immune and neuroendocrine systems cross-talk by using similar ligands and receptors. In this context, the thymus-hypothalamus/pituitary axis can be regarded as a paradigm of connectivity in both normal and pathological conditions. For example, cytokines and thymic hormones modulate hypothalamic-pituitary functions: (a) interleukin (IL)-1 seems to upregulate the production of corticotropin-releasing factor and by adrenocorticotropin by hypothalamic neurons and pituitary cells, respectively; (b) thymulin enhances LH secretion. Conversely, a great deal of data strongly indicate that the hypothalamic-pituitary axis plays a role in the control of thymus physiology. Growth hormone (GH) for example, enhances thymulin secretion by thymic epithelial cells (TEC), both in vivo and in vitro, also increasing extracellular matrix-mediated TEC/thymocyte interactions. Additionally, gap junction-mediated cell coupling among TEC is upregulated by ACTH. In a second vein, it was shown that GH injections in aging mice increased total thymocyte numbers and the percentage of CD3-bearing cells, as well concanavalin-A mitogenic response and IL-6 production. In addition to mutual effects, thymus-pituitary similarities for cytokine and hormone production have been demonstrated. Cytokines such as IL-1, IL-2, IL-6, interferon-gamma, transforming growth factor-beta and others can be produced by hypothalamic and/or pituitary cells. Conversely, hormones including GH, PRL, LH, oxytocin, vasopressin and somatostatin can be produced intrathymically. Moreover, receptors for various cytokines and hormones are expressed in both the thymus and the hypothalamus/pituitary axis. Lastly, it is noteworthy that a thymus-pituitary connectivity can also be seen under pathological situations. In this regard, an altered HPA axis has been reported in AIDS, human falciparum malaria and murine rabies, that also show a severe thymic atrophy.
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PMID:Immunoneuroendocrine connectivity: the paradigm of the thymus-hypothalamus/pituitary axis. 987 43

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