Sandin J, Georgieva J, Silberring J, Terenius L
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Neuroreport. 1999 Jan 18;10(1):71-6. doi: 10.1097/00001756-199901180-00014.
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.
利用与电喷雾电离质谱联用的尺寸排阻色谱法，研究了新发现的阿片受体样1（ORL1）受体的内源性配体——阿片样肽孤啡肽（痛敏肽）在大鼠海马体中的体内代谢情况。结果表明，孤啡肽在体内逐步代谢为片段（1-13）和（14-17）以及（1-9）和（10-13）。有趣的是，（1-13）和（1-9）片段具有相同的C端，即精氨酸-丙氨酸-赖氨酸，这表明这是一种酶识别的基序，该酶会在两个连续步骤中将该肽切断。在孤啡肽具有活性的条件下，将（1-13）片段注射到大鼠海马体中对空间学习或运动功能没有影响，这表明这种代谢转化降低了对ORL-1受体的亲和力。
