Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Br J Pharmacol. 1993 Jun;109(2):293-8.

Differential effects of cocaine and cocaethylene on intracellular Ca2+ and myocardial contraction in cardiac myocytes.

Author information

  • 1Harvard-Thorndike Laboratory, Beth Israel Hospital, Harvard Medical School, Boston, MA.

Abstract

1. Isolated cardiac myocytes of the ferret were used to investigate the influence of cocaine and cocaethylene on the intracellular Ca2+ transient indicated by the indo-1 405/480 nm ratio signal, and peak cell shortening. 2. Both cocaine and cocaethylene produced significant decreases in peak intracellular Ca2+ and peak cell shortening in a dose-dependent manner. Of interest, (1) the minimally effective dose of cocaethylene was ten fold lower (10(-8)M versus 10(-7)M) than that of cocaine; (2) the log EC50 of cocaethylene was -5.99 +/- 0.13 (1.0 x 10(-6) M), which was about ten fold lower than that of cocaine (-5.02 +/- 0.11, 9.6 x 10(-6) M); and (3) 1 x 10(-4)M cocaethylene decreased the contraction amplitude by 71 +/- 7%, while the same concentration of cocaine decreased the amplitude only by 55 +/- 5%, indicating that cocaethylene is more potent than cocaine. 3. The negative inotropic effects of either cocaine or cocaethylene could be overcome by noradrenaline (approximately 5 microM) or calcium. 4. In contrast to cocaine, cocaethylene shifted the peak [Ca2+]i-peak shortening relationship downward, indicating that cocaethylene decreased myofilament Ca(2+)-responsiveness. 5. These data indicate that both cocaine and cocaethylene act directly on cardiac myocytes to produce a negative inotropic effect that is due to decreased Ca2+ availability. In contrast to cocaine, cocaethylene produces more potent inhibition by an additional action to decrease myofilament Ca(2+)-responsiveness.

PMID:
8358533
[PubMed - indexed for MEDLINE]
PMCID:
PMC2175707
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk