[3H]-nociceptin ligand-binding and nociceptin opioid receptor mRNA expression in the human brain

Following the cloning of the novel nociceptin opioid receptor (NOP1) and the identification of its endogenous ligand orphanin FQ/nociceptin the distribution and functional role of the NOP1 receptor system have been studied mainly in the rodent CNS. In the present study the regional distribution and splice variant expression of the NOP1 receptor was investigated in the adult human brain using [H-3]-nociceptin autoradiography, NOP1 reverse transcriptase PCR and mRNA in situ hybridization. Ligand binding revealed strong expression of functional NOP1 receptors in the cerebral cortex and moderate signals in hippocampus and cerebellum. Interestingly, the NOP1 receptor specific ligand was also strongly bound in the human striatum. A matching pattern of mRNA expression was observed with high amounts of NOP1 mRNA in the prefrontal and cingulate cortex as well as in the dentate gyrus of the hippocampus. mRNA levels in the Ammon's horn and cerebellar cortex were moderate and low in the striatum. A considerable expression of N-terminal NOP1 splice variant mRNAs was not detectable in the human brain by means of in situ hybridization. This suggests that functional NOP1 receptors in the human brain are encoded by N-terminal full length NOP1 transcripts. The present data on the anatomical distribution of nociceptin binding sites and NOP1 receptor mRNA contribute to the knowledge about opioid receptor systems in the human brain and may promote the understanding of function and pharmacology of the orphanin FQ/nociceptin receptor system in the human CNS. (C) 2003 Published by Elsevier Ltd on behalf of IBRO.