Document Detail


Chronic treatment with dexmedetomidine desensitizes alpha 2-adrenergic signal transduction.
MedLine Citation:
PMID:  9164555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tolerance to the hypnotic response was induced in rats by chronically infusing dexmedetomidine, a novel alpha 2-adrenergic agonist. The alpha 2-adrenoceptor affinity for dexmedtomidine and para-iodoclonidine was significantly reduced in tolerant rats, while Bmax was uncharged. The ability of pertussis toxin (PTX) to ribosylate guanine nucleotide regulatory proteins (G proteins) ex vivo was reduced in tolerant rats; the quantity of PTX-sensitive G proteins was unchanged. Forskolin-stimulated adenylyl cyclase was less sensitive to inhibition by dexmedetomidine in the tolerant rats; however, acute intraperitoneal injection of dexmedetomidine still reduced cyclic adenosine monophosphate levels in tolerant rats. Both the decrease in ribosylation and the lower alpha 2-adrenoceptor binding affinity may reflect a decrease in the ability of the G protein to couple to the alpha 2-adrenoceptors in the locus coeruleus of tolerant rats. In this state, the alpha 2 adrenoceptors are less capable of transducing the effector response (inhibition of adenylyl cyclase).
Authors:
K Reid; Y Hayashi; J Hsu; P A Maguire; B C Rabin; T Z Guo; M Maze
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  57     ISSN:  0091-3057     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:    1997 May-Jun
Date Detail:
Created Date:  1997-07-30     Completed Date:  1997-07-30     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  63-71     Citation Subset:  IM    
Affiliation:
Department of Anesthesia, Stanford University, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Adenylate Cyclase Toxin*
Adrenergic alpha-Agonists / pharmacology*
Animals
Cyclic AMP / metabolism
Drug Evaluation, Preclinical
Drug Tolerance
GTP-Binding Proteins / metabolism
Hypnotics and Sedatives / pharmacology*
Imidazoles / pharmacology*
Infusion Pumps, Implantable
Medetomidine
Pertussis Toxin*
Radioligand Assay
Rats
Receptors, Adrenergic, alpha-2 / agonists*,  metabolism
Signal Transduction / drug effects*
Time Factors
Virulence Factors, Bordetella / pharmacology*
Chemical
Reg. No./Substance:
0/Adenylate Cyclase Toxin; 0/Adrenergic alpha-Agonists; 0/Hypnotics and Sedatives; 0/Imidazoles; 0/Receptors, Adrenergic, alpha-2; 0/Virulence Factors, Bordetella; 60-92-4/Cyclic AMP; 86347-14-0/Medetomidine; EC 2.4.2.31/Pertussis Toxin; EC 3.6.1.-/GTP-Binding Proteins; EC 4.6.1.1/Adenylate Cyclase

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


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