Cortistatin (neuropeptide) explained

Precortistatin is a protein that in humans is encoded by the CORT gene.^{[1] [2]} The 105 amino acid residue human precortistatin in turn is cleaved into cortistatin-17 and cortistatin-29. Cortistatin-17 is the only active peptide derived from the precursor.^[1] Cortistatin (or more specifically cortistatin-17) is a neuropeptide that is expressed in inhibitory neurons of the cerebral cortex, and which has a strong structural similarity to somatostatin. Unlike somatostatin, when infused into the brain, it enhances slow-wave sleep. It binds to sites in the cortex, hippocampus and the amygdala.

Function

Cortistatin is a neuropeptide with strong structural similarity to somatostatin (both peptides belong to the same family). It binds to all known somatostatin receptors, and shares many pharmacological and functional properties with somatostatin, including the depression of neuronal activity. However, it also has many properties distinct from somatostatin, such as 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.^[2]

Further reading

• Spier AD, de Lecea L . Cortistatin: a member of the somatostatin neuropeptide family with distinct physiological functions. . Brain Res. Brain Res. Rev. . 33 . 2–3 . 228–41 . 2001 . 11011067 . 10.1016/S0165-0173(00)00031-X . 14657640 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery. . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Fukusumi S, Kitada C, Takekawa S . Identification and characterization of a novel human cortistatin-like peptide. . Biochem. Biophys. Res. Commun. . 232 . 1 . 157–63 . 1997 . 9125122 . 10.1006/bbrc.1997.6252 . etal.
• Puebla L, Mouchantaf R, Sasi R . Processing of rat preprocortistatin in mouse AtT-20 cells. . J. Neurochem. . 73 . 3 . 1273–7 . 1999 . 10461921 . 10.1046/j.1471-4159.1999.0731273.x . 11290164 . etal.
• Ejeskär K, Abel F, Sjöberg R . Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma consensus deletion region 1p36.3→p36.2, but absence of mutations in primary tumors. . Cytogenet. Cell Genet. . 89 . 1–2 . 62–6 . 2000 . 10894940 . 10.1159/000015566 . 13005311 . etal.
• Deghenghi R, Papotti M, Ghigo E, Muccioli G . Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland. . J. Endocrinol. Invest. . 24 . 1 . RC1–3 . 2001 . 11227737 . 10.1007/bf03343800. 30072435 .
• Harrington JJ, Sherf B, Rundlett S . Creation of genome-wide protein expression libraries using random activation of gene expression. . Nat. Biotechnol. . 19 . 5 . 440–5 . 2001 . 11329013 . 10.1038/88107 . 25064683 . etal.
• Broglio F, Arvat E, Benso A . Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans. . J. Clin. Endocrinol. Metab. . 87 . 8 . 3783–90 . 2002 . 12161511 . 10.1210/jc.87.8.3783 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Dalm VA, van Hagen PM, van Koetsveld PM . Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system. . J. Clin. Endocrinol. Metab. . 88 . 1 . 270–6 . 2003 . 12519865 . 10.1210/jc.2002-020950 . etal. free . 1765/10051 . free .
• Dalm VA, van Hagen PM, van Koetsveld PM . 7954897 . Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells. . Am. J. Physiol. Endocrinol. Metab. . 285 . 2 . E344–53 . 2003 . 12684217 . 10.1152/ajpendo.00048.2003 . etal.
• Robas N, Mead E, Fidock M . MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. . J. Biol. Chem. . 278 . 45 . 44400–4 . 2004 . 12915402 . 10.1074/jbc.M302456200 . free .
• Clark HF, Gurney AL, Abaya E . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 . etal.
• Papotti M, Tarabra E, Allia E . Presence of cortistatin in the human pancreas. . J. Endocrinol. Invest. . 26 . 8 . RC15–8 . 2004 . 14669820 . 10.1007/bf03347348. 32817369 . etal.
• Hernández C, Carrasco E, Casamitjana R . Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects. . Diabetes Care . 28 . 8 . 1941–7 . 2005 . 16043736 . 10.2337/diacare.28.8.1941 . etal. free .

Notes and References

1. de Lecea L, Ruiz-Lozano P, Danielson PE, Peelle-Kirley J, Foye PE, Frankel WN, Sutcliffe JG . 24935564 . Cloning, mRNA expression, and chromosomal mapping of mouse and human preprocortistatin . Genomics . 42 . 3 . 499–506 . Sep 1997 . 9205124 . 10.1006/geno.1997.4763 .
2. Web site: Entrez Gene: CORT cortistatin.