Internalization of somatostatin receptors in brain and periphery

Somatostatin (SRIF) is a neuropeptide that acts as an important regulator of both endocrine and exocrine secretion and modulates neurotransmission in the central nervous system (CNS). SRIF also regulates cell proliferation in normal tissues and tumors. The physiological actions of SRIF aremediated by a family of five G protein-coupled receptors, called somatostatin receptor (SST) SST1, SST2, SST3, SST4, SST5. These five receptors share similarmolecular structure and signaling pathways but they displaymarked differences in their anatomical distribution, subcellular localization and intracellular trafficking. The SST subtypes are widely distributed in the CNS and peripheral nervous system, inmany endocrine glands and tumors, particularly of neuroendocrine origin. In this review, we focus on the agonist-dependent internalization and recycling of the different SST subtypes in vivo in the CNS, peripheral organs and tumors. We also discuss the physiological, pathophysiological and potential therapeutic effects of the intracellular trafficking of SST subtypes.