In vivo metabolism of nociceptin/orphanin FQ in rat hippocampus.
The in vivo metabolism of the newly identified endogenous ligand for the ORL1 receptor, the opioid-like peptide nociceptin (orphanin FQ) in rat hippocampus was studied using size-exclusion chromatography linked to electrospray ionization mass spectrometry. The results show that nociceptin is metabolized step-wise in vivo into fragments (1-13) and (14-17) as well as (1-9) and (10-13), respectively. Interestingly, the (1-13) and (1-9) fragments have the same C-terminus, Arg-Ala-Lys, suggesting that this is a motif recognized by an enzyme which fragments the peptide in two consecutive steps. Injection of the (1-13) fragment into rat hippocampus had no effect on spatial learning or motor function under conditions where nociceptin is active, showing that this metabolic conversion reduces affinity for the ORL-1-receptor.
Sandin
J
J
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Georgieva
J
J
Silberring
J
J
Terenius
L
L
D000595:Amino Acid Sequence; D000818:Animals; D002850:Chromatography, Gel; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008969:Molecular Sequence Data; D018847:Opioid Peptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D000097629:Nociceptin
D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin