Somatostatin

Somatostatin [somatotropin release inhibiting factor (SRIF), Ala-Gly-cyclo(Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys)] is a hypothalamic hormone that inhibits the release of growth hormone, insulin, and glucagon. Somatostatin is believed to adopt an overall p-sheet conformation with a 

Hirschmann et al. O s t the University of Pennsylvania reasoned that a nonpeptidyl scaffold based on D-glucose offered an attractive option for the design of an SRIF mimic. The idea was that the sugar could be appropriately substituted to present the critical Phe-Trp-Lys side chains in an appropriate geometric manner. 

Molecular modeling suggested to the authors that the tribenzyl glycoside 71, with substituents at the C-1, C-2, and C-6 positions, may be able to present 

Interestingly, although not designed for this purpose, an acylated analogue from this series of compounds was found to be a potent binder at the substance P (SP) receptor (IC50 = 60 nM). 

Noting that SAR studies had shown that the pharmacophoric elements of the (5-turn sequence Phe-Trp-Lys and a lipophilic residue such as Phe-6 or Phe-11 were important for somatostatin binding, Papageorgiou et a. M at 

The well-known, but fortunately, rare, pituitary dwarfism is due to the lack of growth hormone (somatotropin). Normal growth can be restored by the administration of the hormone during adolescence. In spite of its obvious importance, we can not discuss here the history of growth hormone it is a 

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Somatostatin is a tetradecapeptide of the hypothalamus that inhibits the release of pituitary growth hormone Its ammo acid sequence has been determined by a combination of Edman degradations and enzymic hydrolysis expenments On the basis of the following data deduce the pnmary structure of somatostatin... 

Somatostatin (SS) = somatotropin-releasing inhibiting factor (SRIF). 

Biosynthesis. Somatostatin exists in longer forms in several biological tissues (95,96). One of the longer forms, which has been isolated from porcine intestine, has been characterized as a 28-amino acid peptide (97). Somatostatin is derived from a precursor containing 116 amino acids (98,99). The precursor contains one copy of the somatostatin tetradecapeptide, which is contained within the sequence of the 28-amino acid peptide at the carboxy-terminal end of the precursor. The 28-amino acid somatostatin is preceded by a single Arg residue, while somatostatin 1-14 is preceded by a pair of basic residues. 

Biological Activities and Analogues. Somatostatin exerts some neurotropic actions, eg, as a tranquilizer and as a spontaneous motor activity depressor. It also lengthens barbiturate anesthesia time and induces sedation and hypothermia. These actions are consistent with the strong association between somatostatin and GABA in the primate cerebral cortex, 90—95% of somatostatin-positive ceHs also contain GABA (100). 

Substitution of Trp by D-Trp increased the potency of somatostatin (101). Most other substitutions, however, are deleterious to biological activity. Cychc octapeptide analogues of somatostatin retain high potency one of them, CTOP, is a potent mu-opioid antagonist. 

CGRP is widely distributed throughout the peripheral and central nervous systems and is found ia sensory neurons and ia the autonomic and enteric nervous systems. In many iastances CGRP is co-localized with other neuroregulators, eg, ACh ia motor neurons, substance P, somatostatin, vasoactive intestinal polypeptide (VIP), and galanin ia sensory neurons. It is also present ia the CNS, with ACh ia the parabigeminal nucleus and with cholecystokinin (CCK) ia the dorsal parabrachial area. CGRP functions as a neuromodulator or co-transmitter. 

Neuropeptide Y. Neuropeptide Y [82785 5-3] (NPY) (255) is a 36-amiao acid peptide that is a member of a peptide family including peptide YY (PYY) [81858-94-8, 106338-42-5] (256) and pancreatic polypeptide (PPY) [59763-91-6] (257). In the periphery, NPY is present in most sympathetic nerve fibers, particulady around blood vessels and also in noradrenergic perivascular and selected parasympathetic nerves (66). Neurons containing NPY-like immunoreactivity ate abundant in the central nervous system, particulady in limbic stmctures. Coexistence with somatostatin and NADPH-diaphorase, an enzyme associated with NO synthesis, is common in the cortex and striatum. 

Capsaicin, an active ingredient in red pepper, is well known for its ability to release and deplete substance P in sensory C fibers. However, this action is not specific for substance P, as neurokinin A, calcitonin gene-related peptide (CGRP), and somatostatin also are released. 

DUP996 [105431-72-9] nicotine [54-11-5] antigalanin agents somatostatin [51110-01-0] thyrotropin-releasing hormone [24305-27-9]... 

Indium-111. Kits for labeling using other radionucHdes include two indium-111 compounds. Indium-111 pentetreotide is used for the scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors. For octreotide DTP A, the active agent is suppHed in a lyopbilized kit with gentisic acid, citrate buffer, and inositol. 

Somatostatin [38916-34-6] M 1637.9, [a]p -36 (c 0.57, 1% AcOH). A tetradecapeptide which is purified by gel filtration on Sephadex G-25, eluting with 2N AcOH, and then by liquid partition chromatography on Sepahdex G-25 using n-BuOH-AcOH-H20 (4 1 5) and has Rp= 0.4. It is a brain growth hormone releasing-inhibiting factor which has also been synthesised. [Burgus et al. Proc Natl Acad Sci USA 70 684 1973, Sorantakis and McKinley Biochem Biophys Res Commun 54 234 1973 Hartridt et al. Pharmazie 37 403 1982.]... 

Growth-horm-rel. hormone Cortico tropin-releasing hormone Somatostatin... 

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