Somatostatin (SS), SS receptors and SS analog treatment in tumorigenesis

Somatostatin (SS) is an inhibitory tetradecapeptide hormone with exocrine, endocrine, paracrine, and autocrine activities, which plays an important regulatory role in several cell functions, includin g inhibition of endocrine secretion and cell prolifer ation. Most of the effects of SS and of its currently avai lable analogs are mediated via five different G proteincoupled receptor (GPCRs), codenamed sst 1-5. SS receptors (sst s) are expressed in a tissue- and subtypeselective manner in both normal and neoplastic cell s, and the majority of SS target tissues express multi ple sst s. Recent data suggest that when sst s are coexpressed, they may interact forming homo- and hetero-dimers also with other GPCRs, thus altering their original pharmacological and functional profiles. The format ion of dimers can be not only constitutive, but also li gandpromoted: hence, compounds with high affinity for t he different receptor subtypes can be used to achieve effects elicited by specific dimers. A feature comm on to most GPCRs is the cyclic process of signaling, desensitization, internalization, resensitization, and recycling to the plasma membrane. These events prevent cells from undergoing excessive receptor stimulation or periods of prolonged inactivity. SS receptors differently internalize after agonist bin ding and, specifically, sst 2, sst 3 and sst 5 are internalized to a greater extent than sst 1 or sst 4. sst s are linked to several second messenger systems which are involved in their downstream intracellular response ( i.e., adenylyl cyclase, calcium and potassium ion channels, Na + /H