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)

The processed product of the human gene preprocortistatin, the peptide cortistatin-17 (hCST-17), bears a strong structural resemblance to the peptide somatostatin (SST), which has an identical receptor binding domain. CST has affinity to all known SST receptor (SSTR) subtypes. Expression of both SST and its receptors has been shown in previous studies to have biological and clinical significance in neuroblastomas, with a putative role in tumor differentiation and apoptosis in vivo. In this work we have employed radiation hybrid mapping and BAC physical mapping to map the human preprocortistatin gene (CORT) to chromosome region 1p36.3-->p36.2, close to the genetic marker D1S244. D1S244 defines the centromeric border of the smallest region of overlap of deletion in our primary neuroblastoma material. We have also defined the genomic sequence of the gene by BAC sequencing and found that preprocortistatin consists of two exons divided by a 1-kb intron. Two polymorphic sites, neither of which causes amino acid exchange, have been detected in the coding region of the gene. Expression studies showed that preprocortistatin is expressed in neuroblastomas of all different stages, as well as in ganglioneuromas. Through genomic sequencing we made mutation analyses of exonic sequences in 49 primary neuroblastomas of all different stages, but no mutations could be detected.
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PMID:Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma consensus deletion region 1p36.3-->p36.2, but absence of mutations in primary tumors. 1089 40

Cortistatin is a recently discovered neuropeptide relative of somatostatin named after its predominantly cortical expression and ability to depress cortical activity. Cortistatin-14 shares 11 of the 14 amino acids of somatostatin-14 yet their nucleotide sequences and chromosomal localization clearly indicate they are products of separate genes. Now cloned from human, mouse and rat sources, cortistatin is known to bind all five cloned somatostatin receptors and share many pharmacological and functional properties with somatostatin including the depression of neuronal activity. However, cortistatin also has many properties distinct from somatostatin including induction of slow-wave sleep, apparently by antagonism of the excitatory effects of acetylcholine on the cortex, reduction of locomotor activity, and activation of cation selective currents not responsive to somatostatin. Expression of mRNA encoding cortistatin follows a circadian rhythm and is upregulated on deprivation of sleep, suggesting cortistatin is a sleep modulatory factor. This review summarizes recent advances in our understanding of the neurobiology of cortistatin, examines the similarities and differences between cortistatin and somatostatin, and asks the question: does cortistatin bind to a cortistatin-specific receptor?
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PMID:Cortistatin: a member of the somatostatin neuropeptide family with distinct physiological functions. 1101 Oct 67

Somatostatin (SRIF or SS) is a phylogenetically ancient, multigene family of peptides. SRIF-14 is conserved with identical primary structure in species of all classes of vertebrates. The presence of multiple SRIF genes has been demonstrated in a number of fish species and could extend to tetrapods. Three distinct SRIF genes have been identified in goldfish. One of these genes, which encodes [Pro2]SRIF-14, is also present in sturgeon and African lungfish, and is closely associated with amphibian [Pro2,Met13]SRIF-14 gene and mammalian cortistatin gene. The post-translational processing of SRIF precursors could result in multiple forms of mature SRIF peptides, with differential abundance and tissue- or cell type-specific patterns. The main neuroendocrine role of SRIF-14 peptide that has been determined in fish is the inhibition of pituitary growth hormone secretion. The functions of SRIF-14 variant or larger forms of SRIF peptide and the regulation of SRIF gene expression remain to be explored. Type 1 and type 2 SRIF receptors have been identified from goldfish and a type 3 SRIF receptor has been identified from an electric fish. Fish SRIF receptors display considerable homology with mammalian counterparts in terms of primary structure and negative coupling to adenylate cyclase. Although additional types of receptors remain to be determined, identification of the multiple gene family of SRIF peptides and multiple types of SRIF receptors opens a new avenue for the study of physiological roles of SRIF, and the molecular and cellular mechanisms of SRIF action in fish.
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PMID:Somatostatin family of peptides and its receptors in fish. 1114 81

Antagonism between GH secretagogues (GHS) and somatostatin (SRIH) has been postulated and demonstrated, but SRIH does not bind to GHS receptors (GHS-R) and potent synthetic peptidyl GHS (GHRP6, hexarelin) do not displace radiolabeled SRIH from its receptors. However, non-natural SRIH octapeptide agonists (mainly lanreotide and vapreotide) displace 125I-Tyr-Ala-hexarelin from pituitary binding sites suggesting that an endogenous factor related to SRIH might exist and interact with GHS-R. Our aims were to investigate the ability of different SRIH-like peptides such as various SRIH fragments (SRIH 3-14, SRIH 7-14, SRIH 3-10, SRIH 7-10, SRIH 2-9) and a natural neuropeptide that shows a high structural homology with SRIH such as cortistatin-14 (CST) to compete with 125I-Tyr-Ala-hexarelin for human pituitary binding sites and to compare their binding affinity with that of hexarelin and ghrelin, a gastric-derived peptidyl GHS that has been proposed as a natural ligand of GHS-R. While the binding of 125I-Tyr-Ala-hexarelin to pituitary membranes was completely displaced by unlabelled hexarelin, ghrelin and CST, none of the SRIH fragments tested inhibited this binding. Ghrelin and CST exhibited a similar affinity (4.6-5.4 x 10(-7) mol/l) for the binding while hexarelin was more effective by about four orders of magnitude in displacing 125I-Tyr-Ala-hexarelin. Our data demonstrate for the first time that cortistatin, a natural peptide related to SRIH, binds to GHS-R and suggest that this factor may play a role in modulating the activity of these receptors.
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PMID:Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland. 1122 37

Somatostatin, and the recently discovered neuropeptide cortistatin, exert their physiological actions via a family of six G protein-coupled receptors (sst1, sst2A, sst2B, sst3, sst4, sst5). Following the cloning of somatostatin receptors significant advances have been made in our understanding of their molecular, pharmacological and signaling properties although much progress remains to be done to define their physiological role in vivo. In this review, the present knowledge regarding neuroanatomical localization, signal transduction pathways, desensitization and internalization properties of somatostatin receptors is summarized. Evidence that somatostatin receptors can form homo- and heterodimers and can physically interact with members of the SSTRIP/Shank/ProSAP1/CortBP1 family is also discussed.
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PMID:Cellular biology of somatostatin receptors. 1134 6

A DNA fragment encoding an amino acid sequence possessing common features to the G protein-coupled receptor (GPCR) superfamily was found in the human genomic sequence, and from this information, the full-length cDNA of a novel GPCR, designated SLT, was cloned from the human hippocampus cDNA library. SLT showed the highest homology to the melanin-concentrating hormone (MCH) receptor, SLC-1 (31.5% identity), and to a lesser extent, to the somatostatin (SST) receptor subtypes. MCH exhibited agonistic behavior when applied to the SLT-expressing CHO cells at subnanomolar doses whereas more than 200 known peptides, including SST and cortistatin, did not. These results indicated that MCH is the cognate ligand of the SLT receptor and that this newly cloned GPCR is the second subtype of the MCH receptor. Quantitative polymerase chain reaction analysis of the SLT gene expression in human tissues showed that the SLT receptor is expressed mainly in brain areas including the cerebral cortex, amygdala, hippocampus, and corpus callosum, as well as in a limited number of peripheral tissues. The distribution of the SLT nearly overlapped that of SLC-1, suggesting that some of the neural functions of MCH may be mediated by both of these receptor subtypes.
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PMID:Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. 1135 73

Somatostatin (SRIF) is a multigene family of peptides. SRIF-14 is conserved with identical primary structure in species across the vertebrates. The presence of multiple SRIF genes has been demonstrated in a number of fish species. Notably, three distinct SRIF genes have been identified in goldfish. One of these genes, which encodes [Pro(2)]SRIF-14, has also been identified in sturgeon and African lungfish, and is closely associated with the amphibian [Pro(2),Met(13)]SRIF-14 gene and mammalian cortistatin gene. The main neuroendocrine role of SRIF-14 peptide that has been determined in fish is the inhibition of pituitary growth hormone secretion. The functions of SRIF-14 variant or larger forms of SRIF peptide and the regulation of SRIF gene expression remain to be explored. Type one and two SRIF receptors have been identified from goldfish and type three SRIF receptor from an electric fish. Fish SRIF receptors display considerable homology to mammalian counterparts in terms of primary structure and negative coupling to adenylate cyclase. The identification of the multiple gene family of SRIF peptides and multiple types of SRIF receptors in fish opens a new avenue for the study of physiological roles of SRIF, and the molecular and cellular mechanisms of SRIF actions in fish.
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PMID:Somatostatins and their receptors in fish. 1139 90

Somatostatin (somatotropin release inhibiting factor, SRIF), exerts its effects via specific G protein coupled receptors of which five subtypes have been cloned (sst1-5). Recently, SRIF receptors have also been cloned from fish tissues. In this study, goldfish sst5 receptors (gfsst5) were expressed and characterised in the Chinese hamster lung fibroblast cell line, that harbours the luciferase reporter gene driven by the serum responsive element (CCL39-SRE-Luci). The agonist radioligands [125I]-LTT-SRIF-28 ([Leu8, DTrp22, 125I-Tyr25]SRIF-28) and [125I][Tyr10]cortistatin-14 labelled similar receptor densities with high affinity and in a saturable manner (pKd: 9.99-9.71; Bmax: 300-350 fmol mg-1). 5'-Guanylyl-imidodiphosphate inhibited radioligand binding to some degree (38.5-57.9%). In competition binding studies, the pharmacological profile of SRIF binding sites defined with [125I]LTT-SRIF-28 and [125I][Tyr10]cortistatin-14 correlated significantly (r2=0.97, n=20). Pharmacological profiles of human and mouse sst5 receptors expressed in CCL39 cells correlated markedly less with those of the gfsst5 profile (r2=0.52-0.78, n > or = b16). Functional expression of the gfsst5 receptor was examined by measurement of agonist-induced luciferase expression and stimulation of [35S]GTPgammaS ([35S]guanosine 5'-O-(3-thiotriphosphate) binding. Profiles were similar to those achieved in radioligand binding studies (r2=0.81-0.93, n=20), although relative potency (pEC50) was reduced compared to pKd values. Relative efficacy profiles of luciferase expression and [35S]GTPgammaS binding, were rather divergent (r2=0.48, n=20) with peptides showing full agonism at one pathway and absence of agonism at the other. BIM 23056 (D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2) acted as an antagonist on the effects of SRIF-14 (pKB=6.74 +/- 0.23) on stimulation of [35S]GTPgammaS binding. Pertussis toxin abolished the effect of SRIF-14 on luciferase expression and [35S]GTPgammaS binding suggesting coupling of the receptor to G(i)/G(o) proteins. In summary, the present studies demonstrate that the gfsst5 receptor has a similar pharmacological profile and transductional properties to mammalian sst5 receptors. The difference in efficacy profiles defined using different functional assays suggests numerous, agonist specific, conformational receptor states, and/or ligand-dependent receptor trafficking.
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PMID:Pharmacological characterisation of the goldfish somatostatin sst5 receptor. 1185 97

The peptide somatostatin (SST) is widely synthesized in the brain and periphery and acts through a family of five receptors (SSTR1-5) to exert numerous effects. A gene product related to SST, cortistatin (CST), also interacts with SSTR1-5. Here we have investigated the regulation of SSTR1-5 and of CST in SST knockout (SSTKO) mice. The five SSTRs were quantitated individually by subtype-selective binding analysis, by immunocytochemistry, and by mRNA measurement and showed, in the brain of SSTKO mice, up-regulation of subtypes 1, 2, 4, and 5, and down-regulation of SSTR3. Peripheral tissues displayed both subtype- and tissue-specific changes in SSTR1-5 mRNA levels of expression. Lack of SST did not up-regulate normal CST expression in brain nor did it induce its expression in the periphery. SST-like immunoreactivity, however, was induced in the proximal midgut in SSTKO animals, suggesting intestinal expression of a novel SST-like gene.
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PMID:Brain somatostatin receptors are up-regulated in somatostatin-deficient mice. 1214 48

Cortistatin (CST)-14, a neuropeptide with high homology with somatostatin (SS)-14, binds all sst subtypes but, unlike SS, also ghrelin's receptor. In six normal adults, we studied the effects of CST-14 or SS-14 administration (2.0 micro g/kg/h iv) on: 1) GH and insulin secretion; 2) the GH response to GHRH (1.0 microg/kg i.v.); and 3) the GH, prolactin (PRL), ACTH, cortisol, insulin, and glucose responses to ghrelin (1.0 microg/kg i.v.). CST-14 inhibited GH and insulin secretion (P < 0.01) to the same extent of SS-14. The GH response to GHRH was similarly inhibited (P < 0.01) by either CST-14 or SS-14. Ghrelin released more GH than GHRH (P < 0.01); these responses were similarly inhibited (P < 0.05) by either CST-14 or SS-14, that made ghrelin-induced GH rise similar to that after GHRH alone. Neither CST-14 nor SS-14 modified PRL, ACTH, or cortisol responses to ghrelin. The inhibitory effect of CST-14 and SS-14 on insulin was unaffected by ghrelin that, in turn, reduced insulin secretion per se (P < 0.01). Ghrelin increased glucose levels (P < 0.05); CST-14 and SS-14 did not modify this effect. Thus, CST-14 inhibits both basal and stimulated GH secretion in humans to the same extent of SS-14. The GH-releasing activity of ghrelin seems partially resistant to CST-14 as well as SS-14. CST-14 and SS-14 do not affect PRL and ACTH secretion but, like ghrelin, inhibit insulin secretion; the ghrelin-induced inhibition is not additive with that of CST-14 or SS-14, suggesting a common mechanism of action on beta cell secretion.
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PMID:Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans. 1216 11


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