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)

Primary cultures of neonatal murine brain have been reported to express multiple receptors that regulate adenylate cyclase activity. Since for the most part these results were obtained with mixed cell cultures, it has been difficult to define receptor profiles for specific cell types. With this concern in mind a series of studies has been initiated designed to identify specific receptors present on highly purified, immunocytochemically defined astroglia derived from the cerebral cortices of neonatal rats. In this study the capacity of a variety of peptide hormones to regulate cyclic AMP metabolism in these cells was examined. Fibroblasts derived from the meninges represent a predictable source of contamination in primary CNS culture. Thus, to assign more clearly specific receptors to the astroglial cell population, receptor-mediated regulation of cyclic AMP accumulation was also examined in fibroblasts. Cyclic AMP accumulation in astroglia was stimulated by catecholamines (acting at beta 1-adrenergic receptors), prostaglandin E1, vasoactive intestinal polypeptide, alpha-melanocyte-stimulating hormone, and adrenocorticotropin. Bombesin, luteinizing hormone-releasing hormone, neurotensin, thyrotropin-releasing hormone, somatostatin, secretin, and vasopressin did not significantly increase cyclic AMP levels in these cultures. Catecholamines, acting at alpha 2-adrenergic receptors, and somatostatin inhibited agonist-stimulated cyclic AMP accumulation. In meningeal cell cultures catecholamines (acting at beta 2- and alpha 2-adrenergic receptors) and prostaglandin E1 regulated cyclic AMP levels. However, vasoactive intestinal peptide did not stimulate and somatostatin did not inhibit cyclic AMP accumulation in these cells.
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PMID:Regulation of cyclic AMP accumulation by peptide hormone receptors in immunocytochemically defined astroglial cells. 620 41

In rat pituitary GH3 cells Ca2+ current through L-type channels is reduced by somatostatin. This modulation of channel activity by somatostatin receptors is mediated by a guanine nucleotide-binding regulatory protein (G protein). It is sensitive to pertussis toxin, indicating the involvement of a G(o)- or Gi-type G protein in this pathway. The identity of this G protein was determined by suppressing the expression of endogenous G proteins individually via intranuclear injection of antisense oligonucleotides. This method was applied to GH3 cells to screen several G protein alpha, beta and gamma subunits for their roles in the defined signal transduction pathway. The loss of somatostatin's modulating activity on the voltage-dependent Ca2+ channel after oligonucleotide injection revealed the involvement of G(o) alpha 2 beta 1 gamma 3 to the exclusion of other closely related subtypes.
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PMID:Somatostatin modulates voltage-dependent Ca2+ channels in GH3 cells via a specific G(o) splice variant. 758 46

Various mechanisms have been identified by which hormones and neurotransmitters, interacting with heptahelical receptors, modulate the intracellular Ca2+ concentration in neuronal, endocrine, and neuroendocrine cells. All of them involve heterotrimeric G proteins. Best documented are hormonal stimulations and inhibitions of voltage-dependent Ca2+ channels. Stimulation is caused by agonists interacting with receptors known to induce phosphatidylinositol 4,5-bisphosphate hydrolysis, that is, a PI response. Although the PI response triggers a transient secretion by fast Ca2+ release, the stimulation of Ca2+ channels is assumed to be responsible for prolonged cell responses and for refilling of IP3-sensitive Ca2+ pools after repeated stimulations. Using antisense oligonucleotide microinjection in rat pituitary GH3 cells, Gi2 has been identified as the pertussis toxin-sensitive G protein stimulating Ca2+ channels, whereas Gq/G11 are involved in the concurrent PI response with subsequent protein kinase C activation, which is required for Ca2+ channel stimulation. Inhibitory modulations of Ca2+ channels are assumed to be the basis of inhibitions of transmitter or hormone secretion. Experiments in GH3 cells have revealed that Go subforms composed of alpha o1 x beta 3 x gamma 4 and alpha o2 x beta 1 x gamma 3 are the active G-protein heterotrimers transferring inhibitory signals from muscarinic M4 and somatostatin receptors to the Ca2+ channel, respectively.
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PMID:Heterotrimeric G proteins involved in the modulation of voltage-dependent calcium channels of neuroendocrine cells. 797 80

The peptide hormone somatostatin inhibits glucose-induced insulin secretion in the rat insulinoma RINm5F cells by inhibition of voltage-gated calcium channels. Here we used micro-injection of antisense oligonucleotides directed against subtypes of G-protein subunits to determine the subunit composition involved in somatostatin-induced inhibition of voltage-gated calcium channels in RINmF5 cells. Injection of antisense oligonucleotides annealing to the respective mRNA of G alpha o2, G beta 1 and G gamma 3 reduced the somatostatin-induced inhibition of calcium channels in these cells. Injection of antisense oligonucleotides directed against other G-protein subunits did not, suggesting that in RINm5F cells the somatostatin receptor couples to a G protein of G alpha o2 beta 1 gamma 3 composition. By using a selective agonist of type 2 somatostatin receptors (SSTR 2) NC 8-12, we identified this receptor as the subtype coupling to calcium channels in RINm5F cells.
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PMID:A specific G(o) heterotrimer couples somatostatin receptors to voltage-gated calcium channels in RINm5F cells. 860 23

In cultured noradrenergic neurons from the rat locus coeruleus, application of recombinant G protein beta 1 gamma 2 subunits (30 nM) to the cytoplasmic side induced single channel activity similar to the somatostatin-induced single channel activity of G protein-coupled inward rectifier potassium channels (Kir (G)). In contrast, recombinant GTP gamma S-activated, myristoylated alpha i2 (100 nM) did not activate this brain Kir (G). Application of beta 1 gamma 2 C68S (30 nM or 150 nM), in which the cysteine residue fourth from the carboxyl terminus of gamma 2 was replaced by serine, failed to activate the brain Kir(G). This mutant lacks prenylation which is required for the association of beta gamma subunit with the cell membrane. Thus, our results suggest that the association of beta gamma subunit with the cell membrane is a prerequisite for activating Kir(G) channels.
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PMID:Activation of G protein-coupled inward rectifier K+ channels in brain neurons requires association of G protein beta gamma subunits with cell membrane. 870 63

The beta 3-adrenoceptor (beta 3-AR) agonist SR-58611A {ethyl-[(7s)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]5, 6,7,8-tetrahydronaphth-2-yl]oxyacetate hydrochloride} stimulated somatostatin and gastrin releases in isolated rat gastric antral epithelial cells. Stimulation was a concentration-dependent process with 50% effective concentrations of 2.7 +/- 1.1 and 3.8 +/- 1.9 nM compared with 209 +/- 71 and 230 +/- 51 nM for isoproterenol, respectively. It was inhibited by selective beta-AR antagonists with the following rank order of potency: SR-59230A 3-(2-ethylphenoxy)1-[(1S)-1,2,3,4-tetrahydronaphth- 1-ylamino]-(2S)-2-propranol oxalate; beta 3-AR antagonist > ICI-118551[erythro-(+/-)-1-(7-methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride; beta 2-AR antagonist > CGP-20712A[(+/-)-[2-(3-carbarmoyl-4-hydroxyphenoxy)-et hyl- amino]-3-[4 (1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]- 2-propranol; beta 1-AR antagonist]. Furthermore, specific binding of 125I-cyanopindolol to the isolated cells was demonstrated and was displaced by the beta-AR antagonists according to the same rank order of potency and with apparent dissociation constants consistent with the 50% inhibitory concentrations for SR-58611A-stimulated somatostatin and gastrin releases. In addition, the presence of beta 3-AR mRNA was detected by reverse transcriptase polymerase chain reaction. These findings provide the first evidence for a gastric beta 3-AR mediating catecholamine stimulation of gastrin and somatostatin releases from antral cells.
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PMID:Characterization of a beta 3-adrenoceptor stimulating gastrin and somatostatin secretions in rat antrum. 917 7

1. Using whole-cell and perforated-patch recordings, we have examined the part played by endogenous G-protein beta gamma subunits in neurotransmitter-mediated inhibition of N-type Ca2+ channel current (ICa) in dissociated rat superior cervical sympathetic neurones. 2. Expression of the C-terminus domain of beta-adrenergic receptor kinase 1 (beta ARK1), which contains the consensus motif (QXXER) for binding G beta gamma, reduced the fast (pertussis toxin (PTX)-sensitive) and voltage-dependent inhibition of ICa by noradrenaline and somatostatin, but not the slow (PTX-insensitive) and voltage-independent inhibition induced by angiotensin II. beta ARK1 peptide reduced GTP-gamma-S-induced voltage-dependent and PTX-sensitive inhibition of ICa but not GTP-gamma-S-mediated voltage-independent inhibition. 3. Overexpression of G beta 1 gamma 2, which mimicked the voltage-dependent inhibition by reducing ICa density and enhancing basal facilitation, occluded the voltage-dependent noradrenaline- and somatostatin-mediated inhibitions but not the inhibition mediated by angiotensin II. 4. Co-expression of the C-terminus of beta ARK1 with beta 1 and gamma 2 subunits prevented the effects of G beta gamma dimers on basal Ca2+ channel behaviour in a manner consistent with the sequestering of G beta gamma. 5. The expression of the C-terminus of beta ARK1 slowed down reinhibition kinetics of ICa following conditioning depolarizations and induced long-lasting facilitation by cumulatively sequestering beta gamma subunits. 6. Our findings identify endogenous G beta gamma as the mediator of the voltage-dependent, PTX-sensitive inhibition of ICa induced by both noradrenaline and somatostatin but not the voltage-independent. PTX-insensitive inhibition by angiotensin II. They also support the view that voltage-dependent inhibition results from a direct G beta gamma-Ca2+ channel interaction.
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PMID:On the role of endogenous G-protein beta gamma subunits in N-type Ca2+ current inhibition by neurotransmitters in rat sympathetic neurones. 949 Aug 60

We carried out studies to explore whether neurotransmitters can directly interact with their T-cell-expressed receptors, leading to either activation or suppression of various T-cell functions. Human and mouse T cells were thus exposed directly to neurotransmitters in the absence of any additional molecule, and various functions were studied, among them cytokine secretion, proliferation, and integrin-mediated adhesion and migration. In this review, I describe the effects of four neuropeptides: somatostatin (SOM), calcitonin-gene-related-peptide (CGRP), neuropeptide Y (NPY), and substance P (Sub P), and one non-peptidergic neurotransmitter--dopamine. We found that SOM, NPY, CGRP, and dopamine interact directly with T cells, leading to the activation of beta 1 integrins and to the subsequent integrin-mediated T-cell adhesion to a component of the extracellular matrix. In contrast, Sub P had a reverse effect--full blockage of integrin-mediated T-cell adhesion triggered by a variety of signals. Each of these neurotransmitters exerted its effect through direct interaction with its specific receptor on the T-cell surface, since the effect was fully blocked by the respective receptor-antagonist. Taken together, this set of findings indicates that neurotransmitters can directly interact with T cells and provide them with either positive (integrin-activating, pro-adhesive) or negative (integrin-inhibiting, anti-adhesive) signals. We further found that the above neurotransmitters, by direct interaction with their specific receptors, drove T cells (of the Th0, Th1, and Th2 phenotypes) into the secretion of both typical and atypical ("forbidden") cytokines. These results suggested that neurotransmitters can substantially affect various cytokine-dependent T-cell activities. As a whole, our studies suggest an important and yet unrecognized role for neurotransmitters in directly dictating or modulating numerous T-cell functions under physiological and pathological conditions.
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PMID:Nerve-driven immunity. The direct effects of neurotransmitters on T-cell function. 1126 58


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