PT  - JOURNAL ARTICLE
AU  - Colette T. Dooley
AU  - Christine G. Spaeth
AU  - Ilona P. Berzetei-Gurske
AU  - Karen Craymer
AU  - Indira D. Adapa
AU  - Susan R. Brandt
AU  - Richard A. Houghten
AU  - Lawrence Toll
TI  - Binding and <em>In Vitro</em> Activities of Peptides with High Affinity for the Nociceptin/Orphanin FQ Receptor, ORL1
DP  - 1997 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 735--741
VI  - 283
IP  - 2
4099  - http://jpet.aspetjournals.org/content/283/2/735.short
4100  - http://jpet.aspetjournals.org/content/283/2/735.full
SO  - J Pharmacol Exp Ther1997 Nov 01; 283
AB  - Fifteen hexapeptides having high affinity for the opioid-like receptor ORL1 were identified from a combinatorial library containing more than 52 million different hexapeptides. The five compounds with the highest affinity were characterized further by use of a variety of in vitro models. Binding studies indicated that these five peptides have affinity for ORL1 in the nanomolar range, similar to the recently discovered endogenous ligand called nociceptin and orphanin FQ (N/OFQ). The activity of these compounds was investigated in three different assays: stimulation of [35S]GTPγS binding and inhibition of forskolin-stimulated cAMP accumulation in Chinese hamster ovary cells transfected with ORL1, and inhibition of electrically induced contractions in the mouse vas deferens. In each assay, the five hexapeptides acted as partial agonists. The EC50 values for stimulation of [35S]GTPγS binding and inhibition of cAMP accumulation were in the range of that for N/OFQ, but maximal effects ranged from 70 to 90% of N/OFQ in the cAMP assay, and 30 to 60% of N/OFQ in the GTPγS assay. The positive hexapeptides identified were found to have minimal structural similarity to N/OFQ. The peptides are positively charged, which could enable them to bind to the negatively charged second extracellular loop thought to be a likely binding site for N/OFQ. The American Society for Pharmacology and Experimental Therapeutics