Basic information of Somatostatin

2017-05-25

The Discovery of Somatostatin

Somatostatin (SS) is an endogenous peptide hormone isolated, purified and characterized in 1973 from almost 500,000 sheep hypothalamic fragment. The molecule is a 14-amino acid cyclic peptide, which is an important regulatory peptide hormone, with a broad range of activities. The amino acid sequence of somatostatin was determined by Edman degradation. The peptide was synthesized by solid phase techniques and the biological activity of the synthesized peptide was determined to be identical to that of native (ovine) somatostatin. Later, somatostatin was synthesized by several other groups and its biological activities examined. Gerich et al. Observed in 1974 that somatostatin produced inhibition of postprandial elevations in plasma glucose, glucagon and growth hormone (GH) in juvenile (insulin-dependent) diabetes. This observation sparked the interest of numerous researchers, because of the potential for treatment of diabetes.

 Basic information of Somatostatin

CAT# 10-101-32
Product Name Somatostatin
CAS No. 38916-34-6
Sequence H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH
M.W/Mr. 1637.88
Molecular Formula C76H104N18O19S2

The Forms of Somatostatin

There are two forms of native somatostatin, somatostatin-14 (SS-14), a 14-amino acid cyclic peptide, and somatostatin-28 (SS-28), which differs from somatostatin-14 by a fragment of 14 amino acids at the amino terminus of SS-14. Both biologically active peptides are encoded by a single gene, and their biosynthesis has been elucidated. Both molecules are disulfide-bridged. They derive from the enzymatic cleavage of a large, 92-amino acid biologically inactive precursor, prosomatostatin (Pro-SS), which in turn arises from preprosomatostatin, an 116 amino acid molecule. Pro-SS is subjected to tissue-specific processing, such that SS-14 and SS-28 are differentially represented in various tissues. Depending on the location, different cell types produce differing amounts of both peptides. Pancreatic δ cells, neural cells and peripheral neurons predominantly produce SS-14, while intestinal mucosal cells predominantly produce SS-28 and account for the largest peripheral source of this peptide. A novel gene was identified, called Cortistatin (CST) gives rise to two gene products similar to SS, CST-17 and CST-29. However, the expression of CST has so far been shown to be restricted to the cerebral cortex.

Production of Somatostatin

The secretion of SS can be modulated by a wide variety of stimuli including ions, neurotransmitters, neuropeptides, growth factors and hormones. Some of the agents that stimulate secretion of SS act directly in non-specific manner while others appear to tissue selective in their action or act indirectly through other transmitters to effect SS release. The release of SS from pancreatic cells as well as from neurons occurs following membrane depolarization and an influx of calcium suggesting a common mode of release irrespective of cell type. The effect of nutrients such as glucose and amino acids have been studies in the hypothalamus and the gut. Hypothalamic SS secretion is abrogated by glucose. However, amino acids have no effect on the release. In the pancreas, glucagon and arginine stimulates release of SS pointing to potential regulators of SS secretion in the pancreas. In general, glucagon, neurotensin, bombesin, growth hormone releasing hormone stimulate the release of SS from various sites while opiates and γ-amino butyric acid inhibit secretion of from various sites and tissues. A number of cytokines appear to modulate the secretion as well as synthesis of SS from immune cells. Interferon-γ, and Interleukin-10 have been shown upregulate SS expression in macrophages. In normal breast tissue SS immunoreactivity to detected only in the stroma, while epithelial cells show SS production only after malignant transformation.

Function

Somatostatin is expressed in the central and peripheral nervous systems and various organs, especially in the gastrointestinal tract. It inhibits the secretion of growth hormone (GH), thyroid stimulating hormone (TSH) and prolactin (PRL) from the anterior pituitary and reduces the release of insulin and glucagon from islet cells and amylase secretion from acinar cells of the pancreas. It modulates the release of catecholamines and indoleamines in the brain and in particular is reported to stimulate the release of dopamine in the striatum. Compound SS-28 also inhibits hormone secretion from different organs and regulates neurotransmission. The various effects of somatostatin derive from its inhibitory effects on two key cellular processes: secretion and cell proliferation.

References:

Moore, Sandra Blaj. Design and synthesis of biologically active peptidomimetic somatostatin analogs. University of California, San Diego, 2004.

Murty, Santos B. Drug stability and release kinetics of a somatostatin analogue formulated in polymeric biodegradable microspheres. 2003.

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