Somatostatin

Abstract

1. Somatostatin (SRIF) exerts diverse physiological actions in the body including regulation of hormone and neurotransmitter release and neuronal firing activity. Analogs of SRIF are used clinically to treat tumors and cancers and to block the hypersecretion of growth hormone in acromegaly. 2. The recent cloning of five SRIF receptor subtypes has allowed for the identification of the molecular basis of the cellular actions of SRIF. The ligand binding domains and regions involved in coupling to G proteins and cellular effector systems are being identified and the processes by which SRIF inhibits cell growth and proliferation are being established. Furthermore, subtype selective agonists have been generated which are being used to investigate the specific biological roles of each SRIF receptor subtypes. 3. Such information will be useful in developing a new generation of SRIF drugs that could be employed to treat metabolic diseases, disorders of the gut, cancer and abnormalities in the central nervous system such as epilepsy and Alzheimer's disease.

Fine‐tuning the π–π Aromatic Interactions in Peptides: Somatostatin Analogues Containing Mesityl Alanine

“…(RMSD = 0.3) During the development of short peptide analogues in the 1990s, the structural rigidity of compounds containing the somatostatin pharmacophore was correlated to their affinity for SSTR2. [23] The outstanding affinity of peptide 4 for SSTR2 is in good agreement with its high rigidity. We reasoned that the well-defined conformation that we found for 4 is probably very close to the native conformation of somatostatin when it binds to SSTR2.…”

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

“…Endogenous SST occurs in two biologically active forms: either a 14-or 28-amino acid peptide. SST has been detected in the CNS, PNS, lung, and gastrointestinal tract (672). SST expression appears to be regulated via PKA-dependent phosphorylation of CREB.…”

Somatostatin decreases voltage-gated Ca2+currents in GH3 cells through activation of somatostatin receptor 2

“…The physiological actions are initiated by the interaction between SRIF and specific, membrane-bound, highaffinity somatostatin receptors (SSTRs) on the surface of responsive cells. Five subtypes of SSTRs (SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5) have been identified as G proteincoupled seven-transmembrane domain receptors (28,32). Activation of SSTRs is associated with a reduction in intracellular cAMP levels and intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) and stimulation of protein tyrosine phosphatase (30).…”