Somatostatin receptor pathophysiology in the neuroendocrine system

Abstract

The actions of somatostatin (SRIF) are mediated by specific G protein-coupled receptors, named SRIF receptor (SSTR) subtypes 1, 2, 3 and 5. SRIF binding to SSTR activates a series of second messenger systems, resulting in the inhibition of calcium channels and adenylate cyclase activity, ultimately leading to inhibition of hormone secretion, while stimulation of other second messengers, such as phosphotyrosine phosphatases play a role in the control of cell growth. The SSTR and dopamine receptor families share a 30% sequence homology and appear to be structurally related. The knowledge on the pathophysiology of these two families of G protein-coupled receptors in neuroendocrine tumors has progressively increased due to the new insights in receptor dimerization, internalization and trafficking. Depending on the expression of different SSTRs in tissues, their combinations and interactions affect the functionality of the subtypes expressed and the influence of the microenvironment, the response to ligands and, by consequence, the response to treatment can be very different.

Keywords::

• NET
• pituitary adenomas
• receptor dimerization
• receptor signaling
• somatostatin
• somatostatin analogs
• somatostatin receptors

Financial & competing interests disclosure

The authors were supported by the following pharmaceutical companies: Ipsen, Novartis, Pfizer and Sandoz, and received grants from Ministero dell’Università e della Ricerca (PRIN 2005 no. 2002067251-001 to F Minuto; Fondo per gli Investimenti della Ricerca di Base no. RBAU019TMF_001 to F Minuto). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.