DAMGO, a mu-opioid receptor selective agonist, distinguishes between mu- and delta-opioid receptors around their first extracellular loops.
The structural basis of mu-opioid receptor (OPR) for the specificity in its ligand binding was investigated using chimeric mu/delta-OPRs. Replacement of the region around the first extracellular loop of delta-OPR with the corresponding region of mu-OPR gave the resultant chimeric receptor the similar affinity to DAMGO compared with the native mu-OPR. The reciprocal replacement deprived the high affinity to DAMGO from mu-OPR. These results indicate that the difference(s) in the structure around the first extracellular loop is critical for DAMGO to distinguish between mu- and delta-OPRs. Furthermore, displacement studies revealed that this region is partly involved in the discrimination between mu- and delta-OPRs by other peptidic mu-selective ligands, such as dermorphin, morphiceptin and CTOP, but not by non-peptidic ligands, such as morphine and naloxone.
Onogi
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Minami
M
M
Katao
Y
Y
Nakagawa
T
T
Aoki
Y
Y
Toya
T
T
Katsumata
S
S
Satoh
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D017465:Receptors, Opioid, delta / Q000737:chemistry / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000187:drug effects
D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D011993:Recombinant Fusion Proteins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-