Section 9
Chapter 8,415

DAMGO, a mu-opioid receptor selective agonist, distinguishes between mu- and delta-opioid receptors around their first extracellular loops

Onogi, T.; Minami, M.; Katao, Y.; Nakagawa, T.; Aoki, Y.; Toya, T.; Katsumata, S.; Satoh, M.

Febs Letters 357(1): 93-97


ISSN/ISBN: 0014-5793
PMID: 8001688
Accession: 008414933

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.

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