Effect of cocaine and methylecgonidine on intracellular Ca2+ and myocardial contraction in cardiac myocytes - PubMed (original) (raw)
Comparative Study
Effect of cocaine and methylecgonidine on intracellular Ca2+ and myocardial contraction in cardiac myocytes
L Huang et al. Am J Physiol. 1997 Aug.
Abstract
We evaluated the cardiac effects of the principle pyrolysis product of crack cocaine smoking, methylecgonidine (MEG), in comparison with cocaine. Peak cell shortening and intracellular Ca2+, as detected by the Ca2+ indicator indo 1, were recorded in enzymatically isolated ferret myocytes. Both cocaine and MEG decreased peak cell shortening and peak intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner (10(-8)-10(-4) M). MEG shifted the peak [Ca2+]i-to-peak shortening relationship downward and was more potent than cocaine. Atropine (10(-6) M) upwardly shifted the dose-response curves of MEG, cocaine, and carbachol but not of procaine. The negative inotropic effects of MEG were inhibited by methoctramine, a selective M2 receptor blocker but not by M1 (pirenzepine) or M3 (4-diphenylacetoxy-N-methylpiperidine methiodide) blocking agents. In contrast to cocaine, the effects of large doses of MEG were irreversible over the time course of our experiments, raising the possibility of structural damage. We conclude that MEG acts primarily on M2 cholinergic receptors in the heart to produce acute cardiac intoxication and, in contrast to cocaine, may decrease the myofilament Ca2+ responseness and cause structural damage to myocytes by a direct toxic effect.
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