Pharmacological characterization of endomorphin-1 and endomorphin-2 in mouse brain Journal Article
| Authors: | Goldberg, I. E.; Rossi, G. C.; Letchworth, S. R.; Mathis, J. P.; Ryan-Moro, J.; Leventhal, L.; Su, W.; Emmel, D.; Bolan, E. A.; Pasternak, G. W. |
| Article Title: | Pharmacological characterization of endomorphin-1 and endomorphin-2 in mouse brain |
| Abstract: | The recently isolated peptides endomorphin-1 and endomorphin-2 have been suggested to be the endogenous ligands for the mu receptor. In traditional opioid receptor binding assays in mouse brain homogenates, both endomorphin- 1 and endomorphin-2 competed both mu1 and mu2 receptor sites quite potently. Neither compound had appreciable affinity for either delta or kappa1 receptors, confirming an earlier report. However, the two endomorphins displayed reasonable affinities for kappa3 binding sites, with K(i) values between 20 and 30 nM. Both endomorphins competed 3H-[D-Ala2, MePhe4, Gly(ol)5] enkephalin binding to MOR-1 receptors expressed in CHO cells with high affinity. In mouse brain homogenates 125I-endomorphin-1 and 125-endomorphin-2 binding was selectively competed by mu ligands. 125I-Endomorphin-1 and 125-endomorphin-2 also labeled MOR-1 receptors expressed in CHO cells with high affinity. Autoradiography of the two 125- labeled endomorphins demonstrated regional patterns in the brain similar to those previously observed for mu drugs. Pharmacologically, the endomorphins were potent analgesics. Although they were equipotent supraspinally, endomorphin-1 was more potent spinally. Endomorphin analgesia was effectively blocked by naloxone, as well as the mu-selective antagonists β- funaltrexamine and naloxonazine. In CXBK mice, which are insensitive to supraspinal morphine, neither endomorphin was active, consistent with a mu mechanism of action. Finally, the endomorphins inhibited gastrointestinal transit. In conclusion, these results support the mu selectivity of these agents. |
| Keywords: | controlled study; protein expression; nonhuman; mouse; animals; mice; animal tissue; mice, inbred strains; iodine radioisotopes; brain; analgesics, opioid; pain measurement; oligopeptides; analgesia; mu opiate receptor; receptors, opioid, mu; autoradiography; naloxone; beta funaltrexamine; gastrointestinal transit; cho cell; cho cells; cricetinae; injections, intraventricular; membranes; brain homogenate; male; priority journal; article; endomorphin 1; endomorphin 2 |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 286 |
| Issue: | 2 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 1998-08-01 |
| Start Page: | 1007 |
| End Page: | 1013 |
| Language: | English |
| PUBMED: | 9694962 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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