Dimerization of morphine and orphanin FQ/nociceptin receptors: generation of a novel opioid receptor subtype.
Although orphanin FQ/nociceptin (OFQ/N) receptors are a member of the opioid receptor family of receptors, they bind traditional opioids with very poor affinity. We now demonstrate that mu opioid receptors can physically associate with OFQ/N receptors, resulting in a complex with a unique binding selectivity profile. Immunoprecipitation of epitope-tagged OFQ/N receptors co-precipitates mu receptors. When the two receptors were co-expressed in CHO cells, [3H]OFQ/N retained its high binding affinity for its receptor. However, co-expression of the two receptors increased by up to 250-fold the affinity of a series of opioids in [3H]OFQ/N binding assays. This enhanced affinity was limited to agonists with high affinity for mu receptors. Selective kappa(1) and delta opioids did not lower binding. Despite the dramatic increase in affinity for the opioid agonists in co-expressing cells, the opioid antagonists naloxone and diprenorphine failed to compete [3H]OFQ/N binding.
Pan
Ying-Xian
YX
Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, Weill College of Medicine of Cornell University, 1275 York Avenue, New York, NY 10021, USA.
Bolan
Elizabeth
E
Pasternak
Gavril W
GW
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D019281:Dimerization; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000493:pharmacokinetics; D005822:Genetic Vectors; D009020:Morphine / Q000737:chemistry / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011957:Receptors, Opioid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015183:Restriction Mapping; D014316:Tritium; D000094942:Nociceptin Receptor
D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D011994:Recombinant Proteins; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D000094942:Nociceptin Receptor