Chronic treatment with dexmedetomidine desensitizes alpha 2-adrenergic signal transduction

Pharmacology, Biochemistry, and Behavior
K ReidM Maze

Abstract

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).

References

Dec 1, 1991·Journal of Neurochemistry·R S DumanE J Nestler
Aug 1, 1990·Biochemical Society Transactions·S CollinsR J Lefkowitz
Jan 9, 1989·Brain Research·E J NestlerJ F Tallman
Aug 12, 1988·Science·A Levitzki
Jan 1, 1988·Annual Review of Cell Biology·J L BenovicR J Lefkowitz
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard
Nov 1, 1993·Pharmacology & Toxicology·M Salonen, M Maze
Jan 1, 1994·Brain Research. Molecular Brain Research·M ScheininR T Fremeau
Jan 1, 2013·Lower Urinary Tract Symptoms·Liang-Ming LeeYat-Ching Tong

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Citations

May 25, 2016·Critical Care Nursing Clinics of North America·Gina RiggiSimon Leung

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