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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 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.
AuthorsL Leventhal, L B Stevens, G C Rossi, G W Pasternak, R J Bodnar
JournalThe 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
PMID9316853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Enkephalins
  • Oligonucleotides, Antisense
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naltrexone
  • beta-funaltrexamine
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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