Faculty Collaboration Database

Acute cocaine exposure up-regulates complement expression in rabbit heart. J Pharmacol Exp Ther 2000 Jan;292(1):201-8

Date

12/22/1999

Pubmed ID

10604949

Scopus ID

2-s2.0-0033966847 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

The exact mechanism of the cardiotoxic actions of cocaine remains unclear. The finding that the heart may be a source of injurious complement components led us to investigate whether cocaine promotes myocardial expression of complement. Rabbit isolated hearts were perfused for 70 min with either cocaine hydrochloride (1 or 10 microM), the synthetic isomer (+)-cocaine (10 microM), or procaine hydrochloride (10 or 30 microM). Compared with controls perfused with drug-free buffer, both cocaine and procaine significantly (P <. 05) increased myocardial C1q, C1r, C8, and C9 mRNA expression, whereas 10 microM (+)-cocaine had no effect on complement mRNA expression. Cocaine also significantly increased (P <.05) C3 mRNA transcription. In addition, in vivo administration of cocaine (1 mg/kg) for three consecutive days significantly increased myocardial complement mRNA expression. Cocaine and procaine also increased membrane attack complex (MAC) formation in the myocardium. The antioxidant 2-N-mercaptopropionyl glycine, attenuated the increases in complement mRNA expression induced by 1 microM cocaine and 10 microM procaine. In vivo heparin administration (300 U/kg i.v.), 2 h before removal of the heart and exposure to 1 microM cocaine, did not inhibit C1q, C1r, C3, and C8 mRNA transcription, but decreased MAC expression. It was determined previously that heparin reduces myocardial ischemia/reperfusion injury. Our results suggest that cocaine may cause myocardial injury by up-regulating local complement expression, possibly via the production of reactive oxygen species. Furthermore, the glycosaminoglycan heparin may modulate the cytotoxic effects of cocaine by impeding formation of the MAC.

Author List

Tanhehco EJ, Yasojima K, McGeer PL, Lucchesi BR

Author

Elaine J. Tanhehco MD, PhD Assistant Professor in the Radiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Cocaine
Complement Membrane Attack Complex
Complement System Proteins
Dose-Response Relationship, Drug
Drug Interactions
Heart
Hemodynamics
Heparin
In Vitro Techniques
Liver
Male
Perfusion
Procaine
RNA, Messenger
Rabbits
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Tiopronin
Up-Regulation