Burnside J L, Rodriguez L, Toll L
Neuropharmacology Program, SRI International, 333 Ravenswood Avenue, 94025, Menlo Park, CA, USA.
Peptides. 2000 Jul;21(7):1147-54. doi: 10.1016/s0196-9781(00)00253-9.
Recent studies have identified compounds with reduced efficacy relative to nociceptin/orphanin FQ at the opioid-like receptor ORL1. Utilizing stimulation of [(35)S]GTPgammaS binding as in vitro assays, it was determined that both [Phe(1)psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)NH(2) and the hexapeptide Ac-RYYRIK-NH(2) act as partial agonists in CHO cells transfected with either human or mouse ORL1. Maximal activity for both [Phe(1)psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)NH(2) and Ac-RYYRIK-NH(2) was significantly greater in cells transfected with the human receptor (90% and 73% in a high expressing clone, 76% and 68% in low expressing clone) rather than the mouse receptor (37.5 and 33%), regardless of receptor number in individual clones. In vitro studies in cells transfected with exaggerated receptor numbers can lead to unreliable estimates of agonist and antagonist activity, however, these studies suggest that animal experiments on the activity of novel compounds may not always be better predictors of the ultimate activity in humans.
最近的研究已鉴定出相对于阿片样受体ORL1上的孤啡肽/孤啡肽FQ效力降低的化合物。利用[（35）S]GTPγS结合的刺激作为体外测定，确定了[Phe（1）ψ（CH（2）-NH）Gly（2）]N/OFQ（1-13）NH（2）和六肽Ac-RYYRIK-NH（2）在用人类或小鼠ORL1转染的CHO细胞中均作为部分激动剂。无论单个克隆中的受体数量如何，[Phe（1）ψ（CH（2）-NH）Gly（2）]N/OFQ（1-13）NH（2）和Ac-RYYRIK-NH（2）在用人受体转染的细胞中的最大活性均显著更高（在高表达克隆中分别为90%和73%，在低表达克隆中分别为76%和68%），而不是在小鼠受体中转染的细胞（分别为37.5%和33%）。在用过量受体数量转染的细胞中进行的体外研究可能会导致对激动剂和拮抗剂活性的不可靠估计，然而，这些研究表明，关于新型化合物活性的动物实验可能并不总是人类最终活性的更好预测指标。
