Title: [D-1-Nal(4)]endomorphin-2 is a potent mu-opioid receptor antagonist in the aequorin luminescence-based calcium assay
Authors: Fichna, Jakub ×
Piestrzeniewicz, Mariola
Gach, Katarzyna
Poels, Jeroen
Burgeon, Emmanuel
Vanden Broeck, Jozef
Janecka, Anna #
Issue Date: Aug-2006
Publisher: Pergamon-elsevier science ltd
Series Title: Life Sciences vol:79 issue:11 pages:1094-1099
Abstract: A functional assay, based on aequorin-derived luminescence triggered by receptor-mediated changes in Ca2+ levels, was used to examine relative potency and efficacy of the mu-opioid receptor antagonists. A series of position 3- and 4-substituted endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) analogues containing D-3-(1-naphthyl)-alanine (D-1-Nal) or D-3-(2-naphthyl)-alanine (D-2-Nal), which were previously shown to reverse antinociception induced by endomorphin-2 in the in vivo hot-plate test in mice, was tested in the aequorin luminescence-based calcium assay to examine their g-opioid antagonist potency in vitro. A recombinant mammalian cell line expressing the mu-opioid receptor together with a luminescent reporter protein, apoaequorin, was used in the study. The results obtained in this functional assay indicated that analogues With D-1-Nal or D-2-Nal substitutions in position 4 of endomorphin-2 are strong R-opioid receptor antagonists, while those substituted in position 3 are partial agonists. Exceptional antagonist potency in the calcium assay was observed for [D-1-Nal(4)]endomorphin-2. The pA(2) value for this analogue was 7.95, compared to the value of 8.68 obtained for the universal, non-selective opioid antagonist of the alkaloid structure, naloxone. The obtained results were compared with the data from the hot-plate test in mice. In that in vivo assay [D-1-Nal(4)]endomorphin-2 was also the most potent analogue of the series. (c) 2006 Elsevier Inc. All rights reserved.
ISSN: 0024-3205
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Animal Physiology and Neurobiology Section - miscellaneous
× corresponding author
# (joint) last author

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