Document Detail

Dynorphin A(1-17)-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats.
MedLine Citation:
PMID:  11961051     Owner:  NLM     Status:  MEDLINE    
Ventricular administration of the opioid dynorphin A(1-17) induces feeding in rats. Because its pharmacological characterization has not been fully identified, the present study examined whether a dose-response range of general and selective opioid antagonists as well as antisense oligodeoxynucleotide (AS ODN) opioid probes altered daytime feeding over a 4-h time course elicited by dynorphin. Dynorphin-induced feeding was significantly reduced by a wide range of doses (5-80 nmol i.c.v.) of the selective kappa(1)-opioid antagonist nor-binaltorphamine. Correspondingly, AS ODN probes directed against either exons 1 and 2, but not 3 of the kappa-opioid receptor clone (KOR-1) reduced dynorphin-induced feeding, whereas a missense oligodeoxynucleotide control probe was ineffective. Furthermore, AS ODN probes directed against either exons 1 or 2, but not 3 of the kappa(3)-like opioid receptor clone (KOR-3/ORL-1) also attenuated dynorphin-induced feeding. Although the selective mu-antagonist beta-funaltrexamine (20-80 nmol) reduced dynorphin-induced feeding, an AS ODN probe directed only against exon 1 of the mu-opioid receptor clone was transiently effective. Neither general (naltrexone, 80 nmol) nor delta (naltrindole, 80 nmol)-selective opioid antagonists were particularly effective in reducing dynorphin-induced feeding, and an AS ODN probe targeting the individual exons of the delta-opioid receptor clone failed to significantly reduce dynorphin-induced feeding. These converging antagonist and AS ODN data firmly implicate the kappa(1)-opioid receptor and the KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced feeding.
Robert M Silva; Henya C Grossman; Maria M Hadjimarkou; Grace C Rossi; Gavril W Pasternak; Richard J Bodnar
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  301     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-04-18     Completed Date:  2002-05-13     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  513-8     Citation Subset:  IM    
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MeSH Terms
Dose-Response Relationship, Drug
Drug Interactions
Dynorphins / pharmacology*
Feeding Behavior / drug effects*
Models, Animal
Naltrexone / analogs & derivatives*,  pharmacology
Narcotic Antagonists / pharmacology*
Oligonucleotides, Antisense / pharmacology*
Rats, Sprague-Dawley
Receptors, Opioid / antagonists & inhibitors*,  metabolism
Receptors, Opioid, delta / antagonists & inhibitors,  metabolism
Receptors, Opioid, kappa / antagonists & inhibitors,  metabolism
Receptors, Opioid, mu / antagonists & inhibitors,  metabolism
Grant Support
Reg. No./Substance:
0/Narcotic Antagonists; 0/Oligonucleotides, Antisense; 0/Receptors, Opioid; 0/Receptors, Opioid, delta; 0/Receptors, Opioid, kappa; 0/Receptors, Opioid, mu; 105618-26-6/norbinaltorphimine; 111555-53-4/naltrindole; 5S6W795CQM/Naltrexone; 72782-05-9/beta-funaltrexamine; 74913-18-1/Dynorphins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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