pathophysiology of gpcr homo- and heterodimerization special emphasis on somatostatin receptors病理生理学gpcr homo和heterodimerization特别强调生长激素抑制素受体.pdfVIP

Pharmaceuticals 2012, 5, 417-446; doi:10.3390/ph5050417 OPEN ACCESS Pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Pathophysiology of GPCR Homo- and Heterodimerization: Special Emphasis on Somatostatin Receptors Rishi K. Somvanshi and Ujendra Kumar * Faculty of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada * Author to whom correspondence should be addressed; E-Mail: ujkumar@mail.ubc.ca; Tel.: +1-604-827-3660; Fax: +1-604-822-3035. Received: 3 February 2012; in revised form: 18 April 2012 / Accepted: 19 April 2012 / Published: 27 April 2012 Abstract: G-protein coupled receptors (GPCRs) are cell surface proteins responsible for translating 80% of extracellular reception to intracellular signals. The extracellular information in the form of neurotransmitters, peptides, ions, odorants etc is converted to intracellular signals via a wide variety of effector molecules activating distinct downstream signaling pathways. All GPCRs share common structural features including an extracellular N-terminal, seven-transmembrane domains (TMs) linked by extracellular/intracellular loops and the C-terminal tail. Recent studies have shown that most GPCRs function as dimers (homo- and/or heterodimers) or even higher order of oligomers. Protein-protein interaction among GPCRs and other receptor proteins play a critical role in the modulation of receptor pharmacology and functions. Althou