| Abstract: |
Opioid receptor family is composed of mu, delta and kappa receptors. Another closed related receptor also has been identified, as well as its endogenous ligand orphanin FQ/nociceptin (OFQ/N). Although OFQ/N receptor shows high homology with other opioid receptors, traditional opioids showed poor affinity towards it. Also, the endogenous ligand OFQ/N, displays no significant affinity for mu, kappa or delta opioid receptors. Dimerization is a potential mechanism for modulation of receptor pharmacology and functions. Earlier studies from our lab reported that MOR-1 forms a heterodimer with the mouse ORL1 receptor (KOR-3) that results with a distinct pharmacology. In the heterodimer, 3H-OFQ/N binding is sensitive to traditional mu opioid agonists. However, antagonists do not display the same enhanced ability to block binding. Our laboratory has cloned a number of MOR-1 variants resulting from 3' and/or 5'splicing. We now have examined the physical association of a number of the 3'-splice variants of MOR-1 with the mouse ORL1 receptor (KOR-3) as well as their ligand binding and signaling properties. |
