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μ‐Opioid Receptor Ligands Lack Receptor Subtype Selectivity in the Aequorin Luminescence‐based Calcium Assay
Author(s) -
Fichna Jakub,
Staniszewska Renata,
Poels Jeroen,
Broeck Jozef Vanden,
Janecka Anna
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00550.x
Subject(s) - damgo , chemistry , opioid receptor , receptor , pharmacology , (+) naloxone , agonist , chinese hamster ovary cell , competitive antagonist , receptor antagonist , opioid antagonist , population , opioid , antagonist , medicine , biology , biochemistry , environmental health
The aim of the present study was to characterize the binding selectivity of the μ‐opioid receptor ligands, endomorphin‐1, endomorphin‐2, and DAMGO, in the in vitro functional assay, based on the changes in intracellular calcium levels. For the experiments Chinese hamster ovary cells, stably expressing human μ‐receptor, were used. The μ‐agonist‐induced calcium responses were significantly inhibited by naloxone, an opioid antagonist with high preference for the μ‐opioid receptors. Naloxonazine, a μ 1 ‐non‐peptide antagonist, inhibited the effect of all tested μ‐agonists. However, there was no significant difference in the antagonist effect of naloxonazine on the calcium response induced by μ 1 ‐ (endomorphin‐2) and μ 2 ‐agonists (endomorphin‐1, DAMGO). [ d ‐Pro 2 ]endomorphin‐1 and [ d ‐Pro 2 ]endomorphin‐2, putative peptide μ 2 ‐ and μ 1 ‐antagonists, respectively, which had been shown in vivo to inhibit the antinociception induced by μ‐agonists, produced no inhibitory effect in our in vitro experiments. Our results demonstrated that there is only one population of the μ‐opioid receptors expressed in the Chinese hamster ovary cells. We suggest that the μ‐opioid receptors form a homogenous population in the in vitro systems. However, the existence of μ‐receptor subtypes in vivo is still pharmacologically possible.