Cloning and characterization of the rhesus monkey nociceptin/orphanin FQ receptor

Abstract

We succeeded in cloning the rhesus monkey nociceptin/orphanin FQ peptide (NOP) receptor. The nucleotide sequence and amino acid sequence of the rhesus monkey NOP receptor were 95.9% and 97.8%, respectively, identical to the human NOP receptor. There was no significant difference between the rhesus monkey NOP receptor and the human NOP receptor in the binding affinity of [¹²⁵I] [Thy¹⁴]nociceptin and the binding of [³⁵S]guanosine 5'-O-(γ thio)triphospate ([³⁵S]GTPγS) stimulated by nociceptin/orphanin FQ (N/OFQ). A selective NOP receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one ((+)-J-113397) inhibited the [³⁵S]GTPγS binding activated by N/OFQ using the membrane of the rhesus monkey NOP receptor. The antagonistic activity of (+)-J-113397 to the rhesus monkey NOP receptor was comparable to that to the human NOP receptor. Thus, N/OFQ acts via activation of the NOP receptor in both human and rhesus monkeys without significant species differences.