Grant: Operating Grant

The hormone somatostatin activates a cell by binding to surface receptors that belong to a class of proteins known as G protein coupled receptors (GPCRs). Many other hormones and neurotransmitters also regulate cell function through their own GPCRs of which there are an estimated thousand or more in the body. In general, GPCRs have been thought to function as single molecules or monomers to which a hormone binds. We have found, however, that when a Somatostatin GPCR is activated, it may join up physically with another GPCR belonging to a different family such as a dopamine receptor to form a heterodimers, a novel receptor with enhanced functional activity that is distinct from that of the two separate receptors. We suspect that there are many undiscovered novel receptors like these made up of heterodimers whose properties are different from those of individual monomers. Because of the belief that GPCRs are monomers, our current drugs are aimed at monomers, but if we could design future drugs targeted at any of a number of potential heterodimeric receptor combinations such as dopamine and somatostatin receptors, somatostatin and opioid receptors, somatostatin and epidermal growth factor receptors, we could open the door to new drug treatments for many disorders such as neurological diseases and most importantly in tumor of different origin.