Ebru UZUNHİSARCIKLI, Mükerrem Betül YERER

SOMATOSTATİN ANALOGLARI İLE GÜNCEL TEDAVİ YAKLAŞIMLARI

Somatostatin, hipotalamustan salgılanan ve hipofizden büyüme hormonu salımını inhibe eden bir nöropeptiddir. Somatostatinin yarılanma ömrünün kısa olmasından dolayı çeşitli somatostatin analogları geliştirilmiştir. Somatostatin analogları olan Oktreotid, Vapreotid, Lanreotid ve Pasireotid somatostatin reseptörlerine yüksek afinite ile bağlanan selektif etken maddelerdir. Bu analoglar, pankreatit, akromegali, özofagus varis kanamasının tedavisinde rutin olarak kullanılırken bazı kanser türlerinde ve nörodejeneratif hastalıklarda da faydalı olabileceklerine dair araştırmalar mevcuttur. Bu derleme, somatostatinin biyolojik fonksiyonlarına, reseptörlerine, analoglarına ve potansiyel terapötik kullanımlarına farmakolojik olarak güncel bir görüş sunmaktadır.

Anahtar Kelimeler:

Vapreotid, Oktreotid, nörodejenerasyon, antikanser

CURRENT TREATMENT APPROACHES WITH SOMATOSTATIN

Somatostatin is a neuropeptide that is secreted from the hypothalamus and inhibits the release of growth hormone from the pituitary. Because of the short half-life of somatostatin, various somatostatin analogues have been developed. Octreotide, Vapreotide, Lanreotide and Pasireotide, which are somatostatin analogues, are selective active ingredients that bind to somatostatin receptors with high affinity. While these analogues have been routinely used in the treatment of pancreatitis, acromegaly, esophageal variceal bleeding, there are some researches on these analogues that may also be useful in some types of cancer and neurodegenerative diseases. This review provides a pharmacologically current view of the biological functions, receptors, analogues and potential therapeutic uses of somatostatin.

Keywords:

Vapreotide, Octreotide, neurodegeneration, anticancer,

PDF

___

RxMediaPharma® 2019, İnteraktif İlaç Bilgi Kaynağı. Prof. Dr. Levent Üstünes, (Ed.), Gemaş Yayıncılık.
Perez J, Hoyer D. Co-expression of somatostatin SSTR-3 and SSTR-4 receptor messenger RNAs in the rat brain. Neuroscience, 1995; 64(1): 241-253.
Ludvigsen E, Stridsberg M, Taylor JE, Culler MD, Öberg K, Janson ET. Subtype selective interactions of somatostatin and somatostatin analogs with sst 1, sst 2, and sst 5 in BON-1 cells. Medical Oncology, 2004; 21(3): 285-295
Ferjoux G, Bousquet C, Cordelier P, Benali N, Lopez F, Rochaix P, Buscail L, Susini C. Signal transduction of somatostatin receptors negatively controlling cell proliferation. J Physiol Paris, 2000; 94(3): 205-210.
Denwood G, Tarasov A, Salehi A, Vergari E, Ramracheya R, Takahashi H, Nikolaev VO, Seino S, Gribble F, Reimann F, Rorsman P, Zhang Q. Glucose stimulates somatostatin secretion in pancreatic δ-cells by cAMP-dependent intracellular Ca2+ release. J. Gen. Physiol, 2019; 151(9): 1094-1115.
Hoyer D, Lübbert H, Bruns C. Molecular pharmacology of somatostatin receptors. Naunyn Schmiedebergs Arch Pharmacol, 1994; 350(5): 441-453.
https://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary=NCI%20Metathesaurus&code=C0164678, Erişim tarihi: 22.07.2019
Rai U, Thrimawithana TR., Valery C, Young SA. Therapeutic uses of somatostatin and its analogues: current view and potential applications. Pharmacol. Ther, 2015; 152: 98-110.
Banks WA, Schally AV, Barrera CM, Fasold MB, Durham DA, Csernus VJ, Groot K, Kastin AJ. Permeability of the murine blood-brain barrier to some octapeptide analogs of somatostatin. PNAS, 1990; 87(17): 6762-6766.
https://www.drugbank.ca/drugs/DB04894, Erişim tarihi: 10.08.2019
https://www.drugbank.ca/drugs/DB00104, Erişim tarihi: 13.10.2019
Hannon JP, Nunn C, Stolz B et al. Drug design at peptide receptors. J Mol Neurosci, 2002; 18(1-2): 15-27.
Kéri G, Schwab R, Szokoloczi O, Szüts T, Szolcsanyi J. TT-232: An anti-tumour and anti-inflammatory peptide therapeutic in clinical development. International Journal of Peptide Research and Therapeutics, 2005; 11(1): 3-15.
https://www.drugbank.ca/drugs/DB06791, Erişim tarihi: 13.10.2019
https://www.drugbank.ca/drugs/DB06663, Erişim tarihi: 13.10.2019
http://www.chemspider.com/, Erişim tarihi: 13.10.2019
Borbély É, Scheich B, Helyes Z. Neuropeptides in learning and memory. Neuropeptides, 2013; 47(6): 439-450.
Vécsei L, Bollok I, Telegdy G. Intracerebroventricular somatostatin attenuates electroconvulsive shock-induced amnesia in rats. Peptides, 1983; 4, 293– 295.
Nakagawasa O, Hozumi S, Tan-No K, Niijima F, Arai Y. Yasuhara H, Tadano T. Immunohistochemical fluorescence intensity reduction of brain somatostatin in the impairment of learning and memory-related behaviour induced by olfactory bulbectomy. Behav. Brain Res, 2003; 142: 63–67.
Wilson RS, Martin EM. New intrathecal drugs in Alzheimer's disease and psychometric testing. Ann N Y Acad Sci, 1988; 531(1): 180-186.
Dutar P, Vaillend C, Viollet C, Billard JM, Potier B, Carlo AS, Ungerer A, Epelbaum J. Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin receptor knock-out mice. Neuroscience, 2002; 112: 455–466.
Woltering E.A., Watson J.C., Alperin-Lea R.C., Sharma C., Keenan E., Kurozawa D., Barrie R., Somatostatin analogs: angiogenesis inhibitors with novel mechanisms of action, Invest. New Drugs, 1997; 15: 77–86.
Reubi J.C., Horisberger U., Laissue J., High density of somatostatin receptors in veins surrounding human cancer tissue: role in tumor-host interaction?, Int. J. Cancer, 1994; 56: 681–688.