Evidence of alpha 2-adrenoceptor involvement in B[alpha]P induction processes of drug-metabolizing enzymes: the effect of stress

Konstandi, M., Kostakis, D., Johnson, E., Lang, M. A. and Marselos, M. (1998). Evidence of alpha 2-adrenoceptor involvement in B[alpha]P induction processes of drug-metabolizing enzymes: the effect of stress. In: 3rd Xenobiotic Metabolism and Toxicity Workshop of Balkan Countries, Varna, Bulgaria, (491-495). 4-8 October 1997.

Author Konstandi, M.
Kostakis, D.
Johnson, E.
Lang, M. A.
Marselos, M.
Title of paper Evidence of alpha 2-adrenoceptor involvement in B[alpha]P induction processes of drug-metabolizing enzymes: the effect of stress
Conference name 3rd Xenobiotic Metabolism and Toxicity Workshop of Balkan Countries
Conference location Varna, Bulgaria
Conference dates 4-8 October 1997
Journal name European Journal of Drug Metabolism and Pharmacokinetics   Check publisher's open access policy
Place of Publication Paris, France
Publisher Springer
Publication Year 1998
Sub-type Fully published paper
ISSN 0378-7966
Volume 23
Issue 4
Start page 491
End page 495
Total pages 4
Language eng
Formatted Abstract/Summary
Central to the appropriate regulation of behavioral and physiological changes induced by stress are the noradrenergic neuronal systems which have been implicated in a large number of stress-induced pathophysiological states. Endoplasmic reticulum-bound cytochromes (CYPs) play a crucial role in drug metabolism, resulting in deactivation or formation of reactive derivatives. In turn, these products may be responsible for the chemotherapeutic, mutagenic or carcinogenic properties of the parent compound. The present study assesses the effect of a specific α2- adrenoceptor agonist, dexmedetomidine (DEXT), on stress-induced modification of cytochrome activity in rats using a restraint stress model. The results indicated that activation of the α2-adrenoceptor with DEXT did not alter basal hepatic methoxyresorufin 7-dealkylase (MROD). On the other hand, it appeared to enhance MROD in benzo[a]pyrene (B[a]P) treated animals. Of interest was the finding that stress blocked DEXT-induced MROD enhancement in B[α]P- treated rats. In addition, DEXT had no effect on basal hepatic pentoxyresorufin 7-dealkylase (PROD), while it further enhanced the strong induction by B[a]P. Stress was also found to block this effect. Hepatic ethoxyresorufin 7-dealkylase (EROD) activity was strongly increased by B[a]P; this effect was enhanced by DEXT. In contrast, the DEXT enhanced induction was further strengthened by stress. These findings suggest that α2-adrenoceptors may modulate the induction of cytochromes CYP1A1, 1A2 and 2B1 by B[a]P in rats and that stress may modify this process. In particular, stress may regulate the inducibility of P4501A1 activity by B[a]P via mechanisms related to α2-adrenoceptors.
Keyword alpha 2-adrenoceptor
Stress
B[alpha]P
Rat
Q-Index Code E1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Conference Paper
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Mon, 30 Nov 2009, 15:04:48 EST