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Novel insights in somatostatin receptor physiology

Division of Experimental Pharmacology and Toxicology, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa 11, 25123 Brescia, Italy and ¹ Institute of Pharmacology and Toxicology, Otto-von-Guericke University, Magdeburg, Germany

(Correspondence should be addressed to G Tulipano; Email: tulipano{at}med.unibs.it)

This paper was presented at a symposium held at the Erasmus Medical Center, Rotterdam, The Netherlands, 2005. The symposium was jointly organized by LJ Hofland, Erasmus Medical Center, and A Colao, Federico II University of Naples, Italy. Ipsen partially supported the publication of these proceedings.

Abstract

The experimental data reviewed in the present paper deal with the molecular events underlying the agonist-dependent regulation of the distinct somatostatin receptor subtypes and may suggest important clues about the clinical use of somatostatin analogs with different pattern of receptor specificity for the in vivo targeting of tumoral somatostatin receptors. Somatostatin receptor subtypes are characterized by differential ß-arrestin trafficking and endosomal sorting upon agonist binding due, at least in part, to the differences in their C-terminal tails. Moreover, the subcellular expression pattern of somatostatin receptor subtypes and their activity in response to agonist treatment are affected by intracellular complements, such as proteins involved in intracellular vesicle trafficking. Different somatostatin analogs may induce distinct conformations of the receptor/ligand complex, preferentially coupled to either receptor signaling or receptor endocytosis.