Neural and endocrine mechanisms of cocaine-induced 70-kDa heat shock protein expression in aorta and adrenal gland.
Cocaine has properties of a physiologic stressor that are reflected by its ability to activate both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. We have previously reported that activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system by restraint and pharmacologic agents induces expression of a set of highly conserved cellular stress response proteins (heat shock proteins, HSP) in the adrenal gland and aorta. In the adrenal gland, HSP expression appears to be mediated by stress-induced increases in adrenocorticotropic hormone whereas expression in the aorta involves noradrenergic neurotransmission. In this report we capitalize on the ability of cocaine to stimulate physiologic stress responses to define further mechanisms regulating HSP70 expression in these tissues. We report the novel observation that cocaine administration induces both adrenal and vascular HSP70 mRNA expression. Elevated HSP70 mRNA was preceded by activation of factors capable of binding to the heat shock transcriptional control element and was followed by an elevation in HSP70 protein. Cocaine significantly increased plasma adrenocorticotrophic hormone whereas hypophysectomy eliminated cocaine-induced expression in the adrenal gland suggesting that in this tissue, the effect of cocaine on HSP70 expression is also mediated via adrenocorticotrophic hormone. In the aorta, depletion of catecholamines by reserpine pretreatment paradoxically augmented cocaine-induced HSP70 expression. Based on these results, it appears that HSP70 expression in the aorta occurs through direct actions of cocaine on vascular cells that are ultimately transduced to activation of the HSP70 gene rather than indirectly through alterations in catecholamine reuptake and release.(ABSTRACT TRUNCATED AT 250 WORDS)
Blake
M J
MJ
Department of Pharmacology and Toxicology, University of North Dakota School of Medicine, Grand Forks.
Buckley
A R
AR
Buckley
D J
DJ
LaVoi
K P
KP
Bartlett
T
T
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D002395:Catecholamines / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D051381:Rats; D017207:Rats, Sprague-Dawley
D002395:Catecholamines; D006360:Heat-Shock Proteins; D009838:Oligodeoxyribonucleotides; D000324:Adrenocorticotropic Hormone; D003042:Cocaine