(3)H-morphine-6β-glucuronide binding in brain membranes and an MOR-1- transfected cell line Journal Article
| Authors: | Brown, G. P.; Yang, K.; Ouerfelli, O.; Standifer, K. M.; Byrd, D.; Pasternak, G. W. |
| Article Title: | (3)H-morphine-6β-glucuronide binding in brain membranes and an MOR-1- transfected cell line |
| Abstract: | Morphine-6β-glucuronide (M6G) is a potent morphine metabolite. In an effort to further explore its mechanisms of action, we synthesized 3H-M6G of high specific activity and examined its binding. Although its affinity toward traditional mu receptors is similar to morphine in binding assays in brain and in Chinese hamster ovary cells stably transfected with MOR-1 M6G is > 100-fold more potent than morphine in analgesic assays. This apparent discrepancy cannot be explained by differing intrinsic activities of the two drugs because both agents are partial agonists with similar efficacies in adenylyl cyclase assays in the transfected cell lines. Behavioral studies have implied the possibility of a distinct M6G receptor. Detailed binding studies in brain tissue reveal evidence for heterogeneity. Nonlinear regression analysis of 3H-M6G saturation studies reveals two components. The lower-affinity component (K(D) = 1.93 ± 0.6 nM) corresponds to labeling of traditional mu receptors. In addition, 3H-M6G labels another site of low abundance with very high affinity (K(D) = 68 ± 7 pM). Competition studies indicate that both sites are relatively mu selective. However, several compounds clearly distinguish between the two sites. These binding studies support the concept of a unique M6G receptor responsible for its analgesic activity. |
| Keywords: | controlled study; genetics; nonhuman; animal cell; animal; metabolism; animals; animal tissue; drug potency; transfection; drug synthesis; physiology; drug receptor binding; genetic transfection; brain; binding site; binding sites; cattle; morphine; analgesia; mu opiate receptor; receptors, opioid, mu; binding competition; naloxone; morphine 6 glucuronide; cho cell; cho cells; cricetinae; binding, competitive; morphine-6-glucuronide; hamster; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; morphine derivative; brain membrane; morphine derivatives; priority journal; article; diprenorphine; drug receptor |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 282 |
| Issue: | 3 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 1997-09-01 |
| Start Page: | 1291 |
| End Page: | 1297 |
| Language: | English |
| PUBMED: | 9316837 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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