PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF A GUINEA-PIG KAPPA-OPIOID (DYNORPHIN) RECEPTOR

A full-length cDNA encoding the guinea pig kappa opioid (dynorphin) re ceptor has been isolated. The deduced protein contains 380 aa and seve n hydrophobic alpha-helices characteristic of the G protein-coupled re ceptors. This receptor is 90% identical to the mouse and rat kappa rec eptors, with the greatest level of divergence in the N-terminal region . When expressed in COS-7 cells, the receptor displays high affinity a nd stereospecificity toward dynorphin peptides and other kappa-selecti ve opioid ligands such as U50,488. It does not bind the mu- and delta- selective opioid ligands. The expressed receptor is functionally coupl ed to G protein(s) to inhibit adenylyl cyclase and Ca2+ channels. The guinea pig kappa receptor mRNA is expressed in many brain areas, inclu ding the cerebellum, a pattern that agrees well with autoradiographic maps of classical guinea pig kappa binding sites. Species differences in the pharmacology and mRNA distribution between the cloned guinea pi g and rat kappa receptors may be worthy of further examination.