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Differential effects of cocaine and cocaethylene on intracellular Ca 24+ and myocardial contraction in cardiac myocytes
Author(s) -
Qiu Zhihua,
Morgan James P.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13569.x
Subject(s) - chemistry , inotrope , intracellular , contraction (grammar) , endocrinology , myocyte , medicine , pharmacology , biochemistry
1 Isolated cardiac myocytes of the ferret were used to investigate the influence of cocaine and cocaethylene on the intracellular Ca 2+ 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 Ca 2+ 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 EC 50 of cocaethylene was −5.99 ± 0.13 (1.0 × 10 −6 m ), which was about ten fold lower than that of cocaine (−5.02 ± 0.11, 9.6 × 10 −6 m ); and (3) 1 × 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 (∼ 5 μ m ) or calcium. 4 In contrast to cocaine, cocaethylene shifted the peak [Ca 2+ ] 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 Ca 2+ availability. In contrast to cocaine, cocaethylene produces more potent inhibition by an additional action to decrease myofilament Ca 2+ ‐responsiveness.