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)

A gene for somatostatin, a mammalian peptide (14 amino acid residues) hormone, was synthesized by chemical methods. This gene was fused to the Escherichia coli beta-galactosidase gene on the plasmid pBR322. Transformation of E. coli with the chimeric plasmid DNA led to the synthesis of a polypeptide including the sequence of amino acids corresponding to somatostatin. In vitro, active somatostatin was specifically cleaved from the large chimeric protein by treatment with cyanogen bromide. This represents the first synthesis of a functional polypeptide product from a gene of chemically synthesized origin.
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PMID:Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin. 41 51

A somatostatin receptor isolated from GH4C1 rat pituitary tumor-derived cells was cleaved with cyanogen bromide or cyanogen bromide+trypsin to obtain sequenceable fragments. Five unique amino acid sequences ranging from 6 to 27 amino acid residues were obtained. The sequence was identical to sequence recently reported for one of two somatostatin receptors cloned from human pancreas [Yamada et al., (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 251-255] except for a single valine to isoleucine substitution. This is the first report of amino acid sequence from a purified somatostatin receptor.
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PMID:Partial amino acid sequence of a somatostatin receptor isolated from GH4C1 pituitary cells. 134 34

In the present study we investigated the effects of modulating endogenous somatostatin (SRIF) on the GH response to growth hormone-releasing hormone (GHRH) in spontaneously diabetic BB/Wor rats and nondiabetic littermates. Plasma growth hormone (GH) concentrations following injection of GHRH (500 ng/kg, i.v.) were measured in the rats after pretreatment with either normal sheep serum+saline (NSS+SAL), somatostatin antibody (SRIF-Ab), or pyridostigmine bromide (PD), an acetylcholine esterase inhibitor hypothesized to decrease hypothalamic SRIF tone. The GH response to GHRH in spontaneous diabetic rats pretreated with NSS+SAL was significantly lower (p less than 0.05) than the response observed in the nondiabetic group. SRIF-Ab pretreatment reversed the blunted GH response observed in the diabetic rats. However, PD pretreatment was not effective. These results indicate that the blunted GH response observed in BB/Wor diabetic rats is reversed by neutralization of endogenous SRIF with SRIF-Ab and leads to the conclusion that SRIF plays an active role in modulating GH secretion in spontaneously diabetic rats. The failure of PD to modulate the GH response suggests this acetylcholine agonist is ineffective in this animal paradigm.
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PMID:Hypothalamic regulation of impaired growth hormone secretion in diabetic rats. 2. Studies in spontaneously diabetic BB Worcester rats. 135 67

A 25-year-old homosexual man with a 2-year history of watery diarrhoea and a 20 kg weight loss is described. He had been diagnosed HIV-1 antibody positive 6 years previously. Investigations excluded opportunist pathogens and other known causes of diarrhoea. A range of anti-diarrhoeal medication had been unsuccessful. Plasma levels of gastrointestinal and pancreatic peptides were normal and treatment with the somatostatin analogue, octreotide, which inhibits release of pancreatic/gut peptides, did not provide any benefit. Cardiovascular autonomic function tests revealed blunted pressor responses but no other abnormalities. Gastric emptying studies with a technetium labelled meal indicated rapid gastric emptying time. This was slowed by the anticholinergic drug, atropine. This suggested increased parasympathetic activity to the gut. He was, therefore, treated with the anti-cholinergic agent, propantheline bromide, which reduced the frequency and volume of stools. He put on weight and has remained well since. This case highlights the diagnostic challenge in HIV-associated chronic diarrhoea, the case for investigations of autonomic function, and the need for a therapeutic trial of anticholinergic drugs, when other measures have failed.
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PMID:Increased gut parasympathetic activity and chronic diarrhoea in a patient with the acquired immunodeficiency syndrome. 142 96

Somatostatin gene fragment extracted and purified from plasmid pSom5 bacterium was ligated with the plasmid pBD2 DNA. Transformation of E. coli D29A1 with the chimeric plasmid DNA led to the synthesis of a polypeptide including the sequence of amino acids corresponding to somatostatin. The chimeric protein (50000 dalton) was purified and characterized by the beta-galactosidase affinity chromatography and the expression of the somatostatin gene in E. coli D29A1 is certain after the radioimmunoassay of the chimeric protein and its mixture by treatment with cyanogen bromide.
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PMID:[Expression of somatostatin gene in E. coli D29A1]. 167 42

The M-current (IM) is a time- and voltage-dependent K+ current that persists at slightly depolarized membrane potentials. IM is reduced by muscarinic cholinergic agonists and certain peptides, and is thought to be responsible in part for the slow and late slow excitatory postsynaptic potentials in sympathetic neurons. Recently, we reported that IM in hippocampal neurons was also augmented by somatostatin-14 and -28 suggesting that two different receptors reciprocally regulate one neuronal channel type. Muscarinic effects on IM may be mediated by various components of the phosphatidylinositol phosphate pathway. We now report the involvement of a different second messenger pathway, that generated by phospholipase A2, in the somatostatin-induced augmentation of IM in hippocampal cells. This pathway generates arachidonic acid from which leukotrienes can be produced by lipoxygenases. We find that the IM-augmenting effects of somatostatin are abolished by two substances that can inhibit phospholipase A2, quinacrine and 4-bromophenacyl bromide, and that both arachidonic acid and leukotriene C4 mimic the effects of somatostatin-14 on hippocampal pyramidal neurons in vitro. Arachidonic and somatostatin effects are blocked by a lipoxygenase inhibitor, implicating an arachidonic acid metabolite, perhaps a leukotriene, in the somatostatin effect.
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PMID:Arachidonic acid metabolites as mediators of somatostatin-induced increase of neuronal M-current. 197 33

The effect of electrical stimulation of the vagus nerves on the release of immunoreactive gastrin-releasing peptide (GRP), gastrin, and somatostatin was investigated using the isolated perfused rat stomach. Electrical stimulation (10 Hz, 1 ms duration, 10 V) of the peripheral end of the subdiaphragmatic vagal trunks produced a significant increase in both GRP and gastrin but a decrease in somatostatin. The infusion of atropine sulfate at a concentration of 10(-5) M augmented GRP release and reversed the decrease in somatostatin release in response to vagal stimulation to an increase above basal levels. However, the gastrin response to vagal stimulation was not affected by atropine. The infusion of hexamethonium bromide at a concentration of 10(-4) M significantly suppressed GRP release but did not affect gastrin secretion in response to vagal stimulation. On the other hand, the somatostatin response to vagal stimulation was completely abolished by hexamethonium. These findings lead us to conclude that the intramural GRP neurons might play an important role in the regulation of gastrin as well as somatostatin secretion and that somatostatin secretion may be controlled not only by a cholinergic inhibitory neuron but also by a noncholinergic, e.g., peptidergic stimulatory neuron, both of which may be regulated through preganglionic vagal fibers via nicotinic receptors. In addition, because the infusion of 10(-7) M GRP suppressed the somatostatin secretion, we suggest that either GRP should be excluded from the list of candidates for the noncholinergic stimulatory neurotransmitter for somatostatin secretion or that there are different mechanisms of action for endogenous and exogenous GRP.
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PMID:Vagal regulation of GRP, gastric somatostatin, and gastrin secretion in vitro. 285 78

The release of prolactin (PRL) from a clonal cell-line of anterior pituitary cells (GH4C1) was inhibited by somatostatin (SRIH) in a dose-dependent manner (ED50 nM). The inhibition (20% of control levels) was detectable within 50 s and maximal within 90 s. Thyroliberin (TRH) enhancement of PRL secretion was biphasic. SRIH inhibited both phases equally. Ionomycin in combination with the phorbol ester, TPA, mimics the TRH-elicited PRL release, and SRIH partly inhibited this effect. SRIH had no effect on TRH-stimulated formation of inositol trisphosphate, and only small effects on TRH-activated adenylate cyclase. Vasoactive intestinal peptide (VIP) and forskolin stimulated cAMP formation and PRL release potently. SRIH inhibited both effects of VIP and forskolin, and there was a close correlation between the inhibition of PRL secretion and cAMP accumulation. 8-Bromo-cAMP enhanced PRL release, an effect that was also partly reduced by SRIH. The Ca2+ channel activator, BAY-K-8644 and high extracellular K+ increased PRL release, and SRIH caused a partial reduction in the release response to both secretagogues. SRIH lowered [Ca2+]i, and markedly reduced the rise in [Ca2+]i elicited by TRH, VIP and K+. SRIH did not influence the Ca2+ spikes recorded in Na+-free solution, and had no effect on the TRH-induced membrane potential changes. Our results demonstrate that SRIH may inhibit PRL release from GH4C1 cells by (1) inhibiting hormone-sensitive adenylate cyclase, (2) blocking the effect of cAMP and (3) lowering [Ca2+]i. None of these effects is, however, sufficient to explain all the effects of SRIH, suggesting that SRIH also exerts a major action at a step subsequent to cAMP accumulation and [Ca2+]i elevation. Since the GH4C1 cells possess one single class of binding sites, this implies that the same SRIH receptor is coupled to several cellular signalling systems.
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PMID:Somatostatin inhibits prolactin secretion by multiple mechanisms involving a site of action distal to increased cyclic adenosine 3',5'-monophosphate and elevated cytosolic Ca2+ in rat lactotrophs. 290 8

The effect of cationic, anionic and nonionic detergents on the EPR spectrum of spin-labeled somatostatin has been studied. At detergent concentrations well above the critical micelle concentration, nonionic detergents do not alter the EPR spectrum. Sodium dodecyl sulfate markedly alters both the line height ratio and the hyperfine splitting constant, whilst dodecyltrimethylammonium bromide alters only slightly the hyperfine splitting constant and line height ratio. The somatostatin-sodium dodecyl sulfate complex appeared monodisperse by sedimentation equilibrium with about 17 g bound detergent per g peptide. Circular dichroic and difference spectra of the dodecyl sulfate-somatostatin complex show that the tryptophanyl residue is buried in a nonpolar environment and that the secondary and tertiary structure of the peptide is markedly altered. Sedimentation equilibrium studies suggest that two types of dodecyltrimethylammonium-somatostatin complex exist. One type resembles the dodecyl sulfate-peptide complex, whilst the other appears to include several peptide units with only about one gram bound detergent per gram peptide.
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PMID:Somatostatin-detergent interaction. 610 70

Messenger RNA from bovine hypothalami was used to direct the synthesis in vitro of a precursor to somatostatin (SRIF) of Mr 15,500. Specific antibodies, raised against the chemically synthesized tetradecapeptide SRIF-14, were used for the preliminary characterization. The radioactively labelled preprosomatostatin was then cleaved by trypsin or cyanogen bromide and the products were assayed by two-dimensional fingerprinting techniques. The results conclusively demonstrated the presence of the tetradecapeptide SRIF-14 sequence and its naturally occurring N-terminally extended form, SRIF-28. This 28-amino-acid sequence was shown to occupy the C terminus of the 15,500-dalton precursor and is probably preceded by basic amino acid(s).
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PMID:Fingerprint analysis of bovine hypothalamic preprosomatostatin. Identification of somatostatin-28 at the C terminus. 613 Sep 42


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