title: Therapeutic uses of somatostatin and its analogues: Current view and potential applications.
abstract: Somatostatin is an endogeneous cyclic tetradecapeptide hormone that exerts multiple biological activities via five ubiquitously distributed receptor subtypes. Classified as a broad inhibitory neuropeptide, somatostatin has anti-secretory, anti-proliferative and anti-angiogenic effects. The clinical use of native somatostatin is limited by a very short half-life (1 to 3min) and the broad spectrum of biological responses. Thus stable, receptor-selective agonists have been developed. The majority of these somatostatin therapeutic agonists bind strongly to two of the five receptor subtypes, although recently an agonist of wider affinity has been introduced. Somatostatin agonists are established in the treatment of acromegaly with recently approved indications in the therapy of neuroendocrine tumours. Potential therapeutic uses for somatostatin analogues include diabetic complications like retinopathy, nephropathy and obesity, due to inhibition of IGF-1, VEGF together with insulin secretion and effects upon the renin-angiotensin-aldosterone system. Wider uses in anti-neoplastic therapy may also be considered and recent studies have further revealed anti-inflammatory and anti-nociceptive effects. This review provides a comprehensive, current view of the biological functions of somatostatin and potential therapeutic uses, informed by the wide range of pharmacological advances reported since the last published review in 2004 by P. Dasgupta. The pharmacology of somatostatin receptors is explained, the current uses of somatostatin agonists are discussed, and the potential future of therapeutic applications is explored.
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, VIC 3083, Australia. Electronic address: umadevi.dojaiprakashrai@rmit.edu.au.
authors.forename: Uma
authors.initials: U
authors.lastname: Rai
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
authors.forename: Thilini R
authors.initials: TR
authors.lastname: Thrimawithana
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
authors.forename: Celine
authors.initials: C
authors.lastname: Valery
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Young
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D017481:Receptors, Somatostatin; D013004:Somatostatin
keywords: Acromegaly; Cancer; Diabetes; Inflammation; Somatostatin; Somatostatin analogues