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)

Glycine (Gly)-extended gastrin has been described as the inactive precursor form of the biologically active amidated gastrin. The ratio of Gly-extended to amidated gastrin is higher in the circulation than in tissue, suggesting either differential secretion and/or metabolism. Although the distribution of the precursor form is similar in tissue and circulation to its amidated product, the significance of measurable levels of precursor peptide in the circulation is unknown. In this study, we have examined the pharmacokinetic properties and organ-specific metabolism of both the Gly-extended and the amidated forms of gastrin-17 (G-17-Gly and G-17-amide) in the conscious sheep. The metabolic clearance rate, half disappearance time, and production rates were similar for both G-17-Gly and G-17-amide. G-17-Gly was extracted across the head, kidney, and lung but not across the gut and liver. Similarly, G-17-amide was extracted across the head, gut, lung, and kidney but not across the liver. G-17-Gly had no biological activity as evidenced by its failure to stimulate somatostatin secretion nor was there any measurable conversion to amidated gastrin in the circulation. We conclude that the presence of G-17-Gly in the circulation is not the result of a slower clearance and that circulating G-17-Gly is not a precursor for circulating gastrin-amide. The results of this study provide important baseline data for understanding the dynamics of the precursor product relationship between G-Gly and G-amide.
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PMID:Pharmacokinetics and organ specific metabolism of glycine-extended and amidated gastrin in sheep. 135 96

By means of radioimmunoassay procedures luteinizing hormone releasing hormone (LHRH)-, Metenkephalin- and somatostatin-like immunoreactivities have been measured in discrete hypothalamic and preoptic nuclei as well as serum luteinizing hormone (LH) levels. Nicotine (2 mg/kg, i.p.) produced after 5 min a significant and selective increase in LHRH-like immunoreactivity in the median eminence and in the medial preoptic nucleus, associated with increases in serum LH levels but without any changes in Met-enkephalin and somatostatin-like immunoreactivities in the median eminence. The results indicate that the nicotine-induced activation of LHRH-immunoreactive neurons involves an enhanced processing of the precursor peptide to LHRH.
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PMID:Nicotine-induced increases in brain luteinizing hormone releasing hormone-like immunoreactivity and in serum luteinizing hormone levels of the male rat. 354 Jul 34

Galanin is a 29 amino-acid peptide originally isolated from porcine intestine. It is synthesized as part of a large precursor peptide the preprogalanin. Immunological studies has showed that there is interspecies conservation of the N terminal portion although the C-terminal portions has a little of immunoreactivity. Galanin has a number of pharmacological properties in whole animals and isolated tissues. Galanin contracts isolated preparation from rat fundus, ileum, colon and urinary bladder. Direct administration of galanin (pGal) into the rat third ventricule stimulates food intake, increases plasma growth hormone and prolactin levels and decrease dopamine levels in the median eminence. Intravenous infusion in dog and humans induce a hyperglycemia and glucose intolerance and inhibits the insulin, somatostatin and pancreatic polipeptide secretion from pancreas. Galanin is a estrogen-stimulated peptide. Estrogens increase dramatically the synthesis of their mRNA and the peptide in the rat pituitary. Galanin-like immunoreactivity is widely distributed in several mamalian species including humans. In the central nervous system it was found in medium emminence, hypothalamus, arcuate nucleus etc. Its localization in neurosecretory granules suggest that galanin functions as a neurotransmitter. The detection of a Gal-immunorectivity in the plasma after 17 beta estradiol stimulation suggests that galanin has a distal target and therefore, may be an additional anterior pituitary hormone. Galanin has been localized in reproductive tissues and this suggests that it may play an estrogen mediated role in the hypothalamic and pituitary function. However, the molecular mechanisms involved in their function remain to be studied.
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PMID:[Galanin, a new neuropeptide. Review]. 875 94

Syntheses of substance P, somatostatin, and calcitonin gene-related peptide in sensory neurons have been suggested to be regulated by neurotrophic factors retrogradely transported from target tissues. In this study, we re-examined this idea by investigating the coexpression of neurotrophin receptor (trk family proto-oncogene) messenger RNAs, and preprotachykinin-A (a precursor peptide of substance P), alpha-calcitonin gene-related peptide and somatostatin messenger RNAs in lumbar dorsal root ganglion neurons by means of in situ hybridization histochemistry in rats. Approximately 35-40%, 5% and 15-20% of sensory neurons displayed signals for trkA, trkB, and trkC messenger RNAs, respectively. Approximately 28% of dorsal root ganglion neurons were positive for preprotachykinin-A messenger RNA, and were divided into two groups; those labeled strongly and those labeled weakly by in situ hybridization. All the strongly-labeled neurons (78% of preprotachykinin-A-positive cells) expressed trkA messenger RNA at the same time, while the weakly-labeled neurons did not. Thirty-seven per cent of dorsal root ganglion neurons expressed alpha-calcitonin gene-related peptide messenger RNA, and most of these neurons (84%) also expressed trkA messenger RNA. No or few preprotachykinin-A messenger RNA- and/or alpha-calcitonin gene-related peptide messenger RNA-expressing neurons were also positive for trkB or trkC messenger RNAs. Nine per cent of dorsal root ganglion neurons expressed somatostatin messenger RNA, and these neurons lacked all three trk messenger RNAs. Furthermore, most of these neurons (about 90%) showed positive, albeit weak, signals for preprotachykinin-A and alpha-calcitonin gene-related peptide messenger RNAs. The results suggest that expression of preprotachykinin-A and alpha-calcitonin gene-related peptide messenger RNAs is mediated by nerve growth factor via trkA receptor but not by brain-derived neurotrophic factor or neurotrophin-3, and that somatostatin gene transcription is not regulated by any member of the neurotrophin family in rat sensory neurons.
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PMID:Coexpression of preprotachykinin-A, alpha-calcitonin gene-related peptide, somatostatin, and neurotrophin receptor family messenger RNAs in rat dorsal root ganglion neurons. 884 23

Somatostatin (SOM) is a 14-amino acid cyclic peptide that regulates granulomatous inflammation. SOM inhibits the release of IFN-gamma from murine granuloma T cells that express SOM receptors. SOM is synthesized as preprosomatostatin (ppSOM), a precursor peptide that is cleaved to release active SOM. In this paper, we demonstrate that granuloma cells express mRNA for this important immunoregulator, and that inflammatory mediators rapidly induce ppSOM mRNA in the splenocytes of uninfected, normal (NL) mice. We developed a sensitive, quantitative PCR assay that measures ppSOM mRNA down to 100 transcripts per microg of total RNA. Dispersed granuloma cells expressed authentic ppSOM mRNA as determined by RT-PCR and cDNA sequencing. The PCR assay readily detected ppSOM mRNA in splenocytes isolated from schistosome-infected mice, but not in splenocytes from NL mice. Splenic ppSOM mRNA expression correlated with the onset of parasite egg deposition and granuloma formation. A 4-h in vitro stimulation with LPS, rIL-10, rIFN-gamma, rTNF-alpha, prostaglandin E2, or dibutyryl cAMP induced ppSOM mRNA in NL splenocytes that otherwise lacked this transcript. Splenocytes from severe combined immunodeficient or recombination activating gene 1-deficient mice expressed ppSOM after exposure to rIL-10, suggesting that neither T nor B cells are necessary for ppSOM mRNA induction. A survey of cell lines demonstrated expression of ppSOM mRNA by P388D1 and J774A.1 macrophage-like cells. These data suggest that SOM, which is probably derived from macrophages, is an inducible component of the innate immune system that regulates T cell IFN-gamma production.
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PMID:Preprosomatostatin messenger RNA is expressed by inflammatory cells and induced by inflammatory mediators and cytokines. 955 8

A large 40-residue precursor peptide (propeptide 5) was synthesized by linking together four designed anticancer peptide analogs to the neuropeptides: vasoactive intestinal peptide, somatostatin, bombesin and substance P, using enzyme cleavable lysyl-lysine linkers. On incubation with the enzyme trypsin, propeptide 5 was cleaved in a sequence-specific manner at the lysyl-lysine residues in the linker to release the individual peptide fragments which were identified by LC-MS. Another precursor peptide (propeptide 5a), consisting of two of the peptide analogs linked through lysyl-lysine linker, was also preferentially cleaved at the Lys-Lys site on incubation with the enzyme trypsin. Propeptide 5 showed potent anticancer activity, both in vitro and in vivo, which was greater than that of the individual component peptides. The enhanced activity suggests that the propeptide is possibly cleaved in the biological system at the lysyl-lysine site to yield the individual peptide analogs, which together show a synergistic effect. On the basis of these experimental findings, it can be concluded that pairs of basic amino acids such as Lys-Lys can be used as facile linkers for delivering multiple biologically active peptides.
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PMID:Delivering multiple anticancer peptides as a single prodrug using lysyl-lysine as a facile linker. 1755 67

Converging evidence suggests a central role for dysfunction of the subgenual anterior cingulate cortex (sgACC) in the pathophysiology of major depressive disorder (MDD). Underlying mechanisms may include altered GABAergic function. Expression of somatostatin (SST), an inhibitory neuropeptide localized to a subset of GABA neurons, has been shown to be lower in the dorsolateral prefrontal cortex of male MDD subjects. Here, to investigate whether alterations in SST may contribute to sgACC dysfunction in MDD, and whether the alterations display sex-specificity, we measured sgACC SST at the mRNA and precursor peptide levels in a large cohort of subjects with MDD. SST mRNA levels were analyzed by quantitative PCR (qPCR) in the postmortem sgACC from male (n=26) and female (n=25) subjects with MDD and sex-matched subjects with no psychiatric diagnosis (n=51). Prepro-SST protein levels were assessed in a subset of subjects (n=42 pairs) by semi-quantitative Western blot. The mRNA expression of SST was significantly reduced by 38% in female subjects and by 27% in male subjects with MDD. The characteristic age-related decline in SST expression was observed in control (Pearson R=-0.357, p=0.005) but not MDD (R=-0.104, p=0.234) subjects, as low expression was detected across ages in MDD subjects. Protein expression was similarly reduced by 19% in both MDD groups, and findings were more robust in female (p=0.0056) than in males (p=0.0373) compared to respective controls. In conclusion, low SST represents a robust pathological finding in MDD. Specifically, alterations in SST signaling and/or SST-bearing GABA neurons may represent a critical pathophysiological entity that contributes to sgACC dysfunction and that matches to the high female vulnerability to develop MDD.
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PMID:Reduced somatostatin in subgenual anterior cingulate cortex in major depression. 2123 2