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 microg; 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 microg) agonist dose, a result consistent with limitations in down-regulation of receptor proteins by antisense. The mu antagonist beta-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.
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Authors | L Leventhal, L B Stevens, G C Rossi, G W Pasternak, R J Bodnar |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 282
Issue 3
Pg. 1402-7
(Sep 1997)
ISSN: 0022-3565 [Print] United States |
PMID | 9316853
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Enkephalins
- Oligonucleotides, Antisense
- Receptors, Opioid, mu
- Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
- Naltrexone
- beta-funaltrexamine
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Topics |
- Animals
- Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
- Enkephalins
(pharmacology)
- Hyperphagia
(chemically induced)
- Male
- Naltrexone
(analogs & derivatives, pharmacology)
- Oligonucleotides, Antisense
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Opioid, mu
(genetics, physiology)
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