κ-Opioid receptors are differentially labeled by arylacetamides and benzomorphans
Using Chinese Hamster Ovary cell membranes that stably expressed the human κ-opioid receptor, we investigated the hypothesis that κ 1- and κ 2-opioid receptors, historically defined by their phrmacological selectivity for either arylacetamides or benzomorphans are, in fact, different affinity states...
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Published in | European journal of pharmacology Vol. 485; no. 1; pp. 119 - 125 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
06.02.2004
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Subjects | |
Online Access | Get full text |
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Summary: | Using Chinese Hamster Ovary cell membranes that stably expressed the human κ-opioid receptor, we investigated the hypothesis that κ
1- and κ
2-opioid receptors, historically defined by their phrmacological selectivity for either arylacetamides or benzomorphans are, in fact, different affinity states or binding sites on the same κ-opioid receptors. Receptor binding studies showed that GTPγS potently inhibited [
3H](5α,7α,8β)-(+)-
N-methyl-
N-(7-[1-pyrrolidinyl]-1-oxaspiro [4.5]dec-8-yl)-benzeneacetamide (U69,593) binding, compared to virtually no inhibition of [
3H]bremazocine binding. Saturation binding experiments showed a three-fold decrease in [
3H]U69,593 affinity in the presence of GTPγS, but GTPγS had no effect on [
3H]bremazocine affinity. The κ-opioid receptor antagonist nor-binaltorphimine had a four-fold higher affinity for [
3H]U69,593-labeled receptors than for [
3H]bremazocine-labeled receptors. Functional selectivity studies, measuring the stimulation of [
35S]GTPγS agonist-induced binding, showed a significantly higher U69,593-induced G protein-receptor activation in comparison to the stimulation observed with bremazocine. These results suggest that pharmacologically defined 1κ-opioid receptor subtypes may be different affinity states of the same receptor. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/j.ejphar.2003.11.078 |