Antisense mapping of the MOR-1 opioid receptor clone: Modulation of hyperphagia induced by DAMGO Journal Article
| Authors: | Leventhal, L.; Stevens, L. B.; Rossi, G. C.; Pasternak, G. W.; Bodnar, R. J. |
| Article Title: | Antisense mapping of the MOR-1 opioid receptor clone: Modulation of hyperphagia induced by DAMGO |
| Abstract: | The mu opioid receptor mediates ingestive behavior: mu-selective agonists stimulate food intake and antagonists reduce intake in many ingestive situations. Antisense oligodeoxynucleotides directed against each of the four exons of the MOR-1 clone were equally effective in reducing spontaneous food intake and body weight in rats. However, antisense probes directed against only exon 1 or 4 of the MOR-1 clone reduced mu-mediated analgesia. The present study examined whether central administration of antisense probes directed against each of the four exons of the MOR-1 clone or a missense control altered hyperphagia elicited by the mu agonist DAMGO across a range of doses. Antisense probes directed against only exon 1 or 4 blocked hyperphagia at agonist doses of 0.5 and 1.0 μg; this pattern was identical to that observed for mu-mediated analgesia. A missense control failed to exert significant effects, which suggests specificity of antisense actions. The effective antisense probes failed to reduce hyperphagia at a higher (5 μg) agonist dose, a result consistent with limitations in down- regulation of receptor proteins by antisense. The mu antagonist β- funaltrexamine produced a similar pattern of effects on mu-mediated hyperphagia. The selective actions of antisense probes directed against different exons of the MOR-1 clone in reducing hyperphagia induced by DAMGO suggest that multiple splice variants of the MOR-1 clone exist and raise the possibility of further opioid receptor subclassifications. |
| Keywords: | controlled study; unclassified drug; exon; dose response; nonhuman; animals; animal experiment; rat; rats; rats, sprague-dawley; mu opiate receptor; receptors, opioid, mu; beta funaltrexamine; naltrexone; oligonucleotides, antisense; enkephalin, ala(2)-mephe(4)-gly(5)-; antisense oligodeoxynucleotide; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; oligonucleotide probe; intracerebroventricular drug administration; male; priority journal; article; hyperphagia; enkephalins; mu opiate receptor mor 1 |
| 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: | 1402 |
| End Page: | 1407 |
| Language: | English |
| PUBMED: | 9316853 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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