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)

Regulatory GTP-binding proteins (G proteins) are membrane-attached heterotrimers (alpha, beta, gamma) that mediate cellular responses to a wide variety of extracellular stimuli. They undergo a cycle of guanine-nucleotide exchange and GTP hydrolysis, during which they dissociate into alpha-subunit and beta gamma complex. The roles of G-protein alpha-subunits in these processes and for the specificity of signal transduction are largely established; the beta- and gamma-subunits are essential for receptor-induced G-protein activation and seem to be less diverse and less specific. Although the complementary DNAs for several beta-subunits have been cloned, isolated subunits have only been studied as beta gamma complexes. Functional differences have been ascribed to the gamma-subunit on the basis of extensive sequence similarity among beta-subunits and apparent heterogeneity in gamma-subunit sequences. Beta gamma complexes can interact directly or indirectly with different effectors. They seem to be interchangeable in their interaction with pertussis toxin-sensitive alpha-subunits, so we tested this by microinjecting antisense oligonucleotides into nuclei of a rat pituitary cell line to suppress the synthesis of individual beta-subunits selectively. Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels.
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PMID:Different beta-subunits determine G-protein interaction with transmembrane receptors. 132 98

Somatostatin-like immunoreactivity was localised immunohistochemically in perivascular nerves in the rabbit central ear artery. Whilst somatostatin had no direct action on this vessel, it significantly inhibited noradrenaline-induced, but not alpha, beta-methylene ATP-induced, vasoconstriction. Somatostatin also inhibited contractions elicited by electrical field stimulation showing greater effect at low (16 Hz) compared with high (64 Hz) frequencies, and inhibited the release of tritiated noradrenaline in a concentration-dependent manner. These results confirm that somatostatin is a neuroregulatory peptide, and suggest that it is modulating vascular sympathetic cotransmission of the rabbit central ear artery by acting both prejunctionally to inhibit transmitter release, and postjunctionally to reduce the action of noradrenaline.
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PMID:Somatostatin modulates vascular sympathetic neurotransmission in the rabbit ear artery. 167 16

1. The intracellularly-recorded electrical and mechanical responses to field stimulation of intramural nerves in three sympathetically-innervated smooth muscles--the mouse vas deferens, the rabbit ear artery and the rabbit mesenteric bed preparation were investigated. 2. In each tissue there was evidence for co-transmission involving noradrenaline (NA) and adenosine 5'-triphosphate (ATP) or a closely related nucleotide. 3. The electrical response in each tissue consisted of excitatory junction potentials (ejps) which were abolished by alpha, beta-methylene ATP (alpha, beta MeATP, 1-10 X 10(-6) M), suggesting that they were mediated by ATP. Only in the rabbit ear artery was there an additional electrical event mediated by NA. This took the form of a small slow membrane depolarization which followed the ejps and which was antagonized by either of the alpha-adrenoreceptor blocking agents phentolamine (1 X 10(-6) M) or prazosin (1 X 10(-7) M). 4. In the mouse vas deferens and rabbit mesenteric artery, both transmitter substances (NA and ATP) played a role in the contractile response to field stimulation. In the rabbit ear artery, NA alone appeared to mediate the contractile event. 5. Contractile responses to nerve-released ATP were accompanied by a membrane potential change, whereas those to NA appeared to be mediated largely by a voltage-independent mechanism. 6. In the mouse vas deferens, the ejps and action potentials evoked by field stimulation appeared to be mediated by a discrete increase in permeability to Na+ and K+. 7. In the mouse vas deferens, local application of bradykinin (1-100 X 10(-7) M) produced a small, slow membrane hyperpolarization. VIP (1-100 X 10(-7) M), neuropeptide Y (1-100 X 10(-7) M), substance P (1-100 X 10(-7) M), somatostatin (1-100 X 10(-7) M), leu-enkephalin (1-100 X 10(-7) M), metenkephalin (1-100 X 10(-7) M) and bombesin (1-100 X 10(-7) M), similarly applied, each produced no significant change in membrane potential. None of these peptides appear to be the transmitter mediating the ejp in this tissue.
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PMID:The electrical and mechanical basis of co-transmission in some vascular and non-vascular smooth muscles. 284 46

Streptozotocin (STZ) was administered to 20 female rhesus monkeys at a dose of between 30 and 55 mg/kg. Depending on the severity of the resultant diabetic-like state, these animals were divided into two groups: insulin-dependent monkeys requiring daily insulin injections and carbohydrate-disturbed animals not requiring insulin. STZ-treated monkeys exhibited significantly higher fasting glucose levels or increased glucose disappearance times after an intravenous glucose tolerance test than did controls. In the insulin-dependent monkeys, fasting plasma glucagon levels were elevated when compared with the carbohydrate-disturubed or control monkeys. Glucagon levels did not differ between carbohydrate-disturbed and control animals. Fasting somatostatin levels were also significantly elevated in insulin-dependent animals when compared with controls. Morphometric analysis was performed on the alpha, beta, and delta cell populations of the pancreatic islets in three control and three diabetic animals. Significant decreases in beta cell percent volume and numerical percent and increases in both alpha and delta cell percent volume and numerical percent were observed in relation to control values after STZ diabetes lasting from 17 to 31 mo. Thus, the diabetic-like state induced by STZ in the monkey resembles juvenile-onset human diabetes mellitus with respect to plasma hormone levels and to morphometric changes in the islets of Langerhans.
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PMID:Streptozotocin diabetes in the monkey: plasma levels of glucose, insulin, glucagon, and somatostatin, with corresponding morphometric analysis of islet endocrine cells. 610 56

The results of a conformational study by 1H and 13C high-resolution NMR at 270 and 500 MHz on the peptide hormone somatostatin have been compared with a series of conformers generated by semi-empirical energy calculations. The use of specifically deuterated phenylalanine residues has enabled us to confirm and supplement the identification of all but the phenylalanine aromatic resonances in the proton spectra of somatostatin. In order to minimize the risk of overlooking some low-energy conformations, four different strategies have been used for the generation of the conformers: two based on combinations of conformations of fragments that had been studied before, one on a random procedure and one on the conformational constraints existing in bicyclic analogs with high biological activity. The experimental values of 3JNH-C alpha H and 3J alpha beta coupling constants and the existence of several ring current shifts allowed us to select from the calculations those families of low-energy conformers that are compatible with the NMR results. The NH temperature coefficients do not warrant the existence of any stable beta or gamma turns in the molecule, although the region SRIF8-12 seems to be the most stable in this respect. In addition there are several upfield shifts: 0.2-0.4 ppm on the Lys9 side-chain, 0.3-0.5 ppm on the Phe6 alpha, beta and Phe7 alpha protons, as well as some 0.2-0.3 ppm shifts on parts of two phenylalanine ring systems. Almost all of these shifts decrease considerably with increasing temperature. Most of the observed NMR results are compatible with the properties of one family of low-energy conformations whose main features are a double beta II bend Trp8-Lys9, Thr10 -Phe11, a close proximity of the Trp8 and Lys9 side chains and an orientation of Phe7 towards the Phe6 alpha, beta protons. We conclude that this set of conformations forms a major contribution to the conformational equilibrium at room temperature. The properties of this and several other sets of low-energy conformations that do not dominate in aqueous solution are discussed in relation to al available experimental evidence.
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PMID:The conformational properties of somatostatin. IV. The conformers contributing to the conformation equilibrium of somatostatin in aqueous solution as found by semi-empirical energy calculations and high-resolution NMR experiments. 612 6

This study investigated the modulating role of glucose on 5 mM arginine stimulation of insulin, somatostatin, and glucagon release from the isolated perfused rat pancreas. As the concentration of glucose was increased linearly from 50 to 300 mg/dl, arginine-stimulated glucagon release was inhibited, with half-maximal inhibition occurring at 84 mg/dl glucose. As glucose increased above 80 mg/dl, somatostatin and insulin release was initiated and they continued to increase in a nearly parallel fashion during the glucose gradient (300 mg/dl). When 5 mM arginine was presented "en block" against varying backgrounds of glucose (30, 60, 75, 90, 120, 150, and 300 mg/dl), glucagon release was diminished in the presence of glucose concentrations greater than 60 mg/dl. Arginine elicited insulin release at all glucose concentrations and was significantly augmented in the presence of glucose greater than 90 mg/dl. Arginine-stimulated somatostatin release was detectable in the 90-mg/dl glucose group and was significantly augmented in the 120- and 150-mg/dl glucose treatment groups. In conclusion, these studies indicate that glucose modulates the arginine effect on alpha, beta, and delta cells; and alpha cells have a lower threshold to glucose than beta and delta cells. Glucose inhibits arginine-stimulated glucagon release in the absence of a detectable glucose or arginine stimulation of somatostatin release. Thus, glucose appears to play a major role in the control of the putative hormonal influence among the islet cells.
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PMID:Dissociation of glucose stimulation of somatostatin and insulin release from glucose inhibition of glucagon release in the isolated perfused rat pancreas. 613 89

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

Protein kinase C [cPKC: alpha, beta (beta I, beta II), gamma], a Ca(2+)- and phospholipid-dependent enzyme, has been thought to play a critical role in the synthesis and secretion of gut hormones in gastrointestinal mucosa. However, the localization of PKC has not yet been clarified at the cellular level in the gastrointestinal epithelium. The present study was made to identify cPKC-containing cells immunohistochemically in the rat duodenal epithelium by light and electron microscopy and by confocal laser scanning microscopy. Special attention was paid to the demonstration of cPKC in basal granulated cells. By light microscopy, some duodenal epithelial cells were demonstrated to be immunopositive for PKC alpha-, beta- and gamma-subspecies. Their distribution and incidence were almost similar to those of cells stained by the silver impregnation method of Grimelius. By electron microscopy, profiles of secretory granules were found at the basal region of the PKC-immunopositive epithelial cells. When the cells were double-immunostained for gastrin, serotonin or somatostatin and for PKC alpha-, beta- or gamma-subspecies, these gut hormones and PKC subspecies were shown to colocalize as examined by confocal laser scanning microscopy. These findings show that cPKC (alpha, beta, gamma) is present in basal granulated cells such as G-, EC- and D-cells, presumably playing some important role in regulation of gut hormones, including their synthesis and/or secretion.
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PMID:Protein kinase C alpha-, beta- and gamma-subspecies in basal granulated cells of rat duodenal mucosa. 764 59

To study the target antigens of the islet cell cytoplasmic antibodies (ICA), we tried to make a monoclonal islet cell antibody. We made a monoclonal antibody 14A20 (IgM, kappa) that reacted strongly with Wistar and BB rat islet cells and weakly with pancreatic acinar cells. The immunoreactivity of the 14A20 was also found to react extensively in neuroendocrine cells. Immunostaining showed a granular pattern in both neurons and islet cells. Chemical and enzymic studies revealed that the antigen has the property of a protein. We compared immunoreactivity of the monoclonal antibody 14A20 with anti-insulin, -glucagon or -somatostatin antibodies. The antigen recognized by the monoclonal antibody 14A20 was equally present in the alpha, beta, and delta cells of islet, which mimicked the immunoreactivity of the ICA in the pancreas. The recognized protein had a relative molecular weight of 220,000, indicating that it is different from the previously identified target antigen of the ICA.
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PMID:Production of a monoclonal antibody 14A20 that reacts with a 220-kDa protein in the islet cells. 791 25

In the adult mouse, pancreatic islets contain four islet cell types: alpha, beta, delta and pancreatic polypeptide cells that synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. The early progenitor cells to the pancreatic islets are multipotential and coactivate all the islet-specific genes from the time they first appear. As development proceeds, expression of islet-specific hormones becomes restricted to the pattern of expression characteristic of mature islet cells. The phenotype of mature islet cells, however, is not stable since different environmental stimuli can induce the reappearance of embryonal traits in mature beta cells.
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PMID:On the origin of pancreatic endocrine cells, proliferation and neoplastic transformation. 821 Sep 49


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