PT  - JOURNAL ARTICLE
AU  - E V Varga
AU  - X Li
AU  - D Stropova
AU  - T Zalewska
AU  - R S Landsman
AU  - R J Knapp
AU  - E Malatynska
AU  - K Kawai
AU  - A Mizusura
AU  - H Nagase
AU  - S N Calderon
AU  - K Rice
AU  - V J Hruby
AU  - W R Roeske
AU  - H I Yamamura
TI  - The third extracellular loop of the human delta-opioid receptor determines the selectivity of delta-opioid agonists.
DP  - 1996 Dec 01
TA  - Molecular Pharmacology
PG  - 1619--1624
VI  - 50
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/50/6/1619.short
4100  - http://molpharm.aspetjournals.org/content/50/6/1619.full
SO  - Mol Pharmacol1996 Dec 01; 50
AB  - In the present study, we replaced the third extracellular loop of the human delta-opioid receptor with that of the human mu-opioid receptor. A modified polymerase chain reaction overlap extension method was used to achieve the exact splicing in the chimera to show the importance of the extracellular loop in ligand binding without interference from transmembrane substitutions. The replacement of the third extracellular loop did not alter the affinity of [3H]diprenorphine but caused a dramatic decrease in the affinity of both the delta-selective peptide agonists cyclo[D-Pen2,4'Cl-Phe4,D-Pen5]enkephalin and deltorphin II and the delta-selective nonpeptide agonists SNC 121 and (-)TAN 67. The affinities of the mu-selective peptide agonist [D-Ala2-MePhe4-Gly-ol5]enkephalin and the mu-preferring nonpeptide agonist morphine were not affected. Site-directed mutagenesis studies show that the mechanism of ligand recognition might be different for each structural class of opioid ligands.