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Interaction of palmitoyl carnitine with calcium antagonists in myocytes
Author(s) -
Patmore Leslie,
Duncan Greig P.,
Spedding Michael
Publication year - 1989
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.1476-5381.1989.tb11971.x
Subject(s) - carnitine , nisoldipine , chemistry , verapamil , medicine , calcium , endocrinology , ouabain , myocyte , diltiazem , pharmacology , biochemistry , nifedipine , sodium , organic chemistry
1 Beating of aggregates of embryonic chick myocytes, in primary culture, was quantified by use of a motion‐detector and video‐recorder technique. Interactions of palmitoyl carnitine, a putative endogenous ligand at Ca 2+ channels, with calcium antagonists were investigated. 2 Bay K 8644 (1–100 n m ) and palmitoyl carnitine (0.2–30 μ m ) increased edge movement of the aggregates; beats fused so that there was an increase in baseline ‘tone’. The concentrations required to produce a 50% increase in edge movement were 2.5 n m for Bay K 8644 and 2 μ m for palmitoyl carnitine. Higher concentrations (20–30 μ m ) of palmitoyl carnitine caused tachycardia of abrupt onset but resulted in cessation of beating. The effects of palmitoyl carnitine were not stereo‐selective in that the (+)− and (−)‐isomers were equieffective. Lysophosphatidyl choline (LPC) had no effect in concentrations up to 10 μ m but higher concentrations caused tachycardia followed by cessation of beating. High concentrations of both palmitoyl carnitine and LPC (100 μ m ) caused break‐up of the aggregates, presumably as a result of detergent effects. 3 Palmitoyl carnitine (1–100 μ m ) reversed the inhibitory effects of nisoldipine (0.3 μ m ), diltiazem (10 μ m ) and verapamil (1 μ m ). Ouabain was ineffective in reversing the effects of nisoldipine, differentiating the effects of palmitoyl carnitine from those of Na + /K + ATPase inhibition. In contrast, palmitoyl carnitine did not reverse the inhibitory effects of pimozide (2 μ m ) or lidoflazine (7 μ m ); palmitoyl carnitine showed a similar profile to Bay K 8644 in this respect. 4 These findings indicate that the effects of palmitoyl carnitine closely resemble those of Bay K 8644 and can be differentiated from those of lysophospholipids. As palmitoyl carnitine accumulates in the sarcolemma during myocardial ischaemia, the mode of action in the Ca 2+ channel may have clinical relevance for the use of calcium antagonists in ischaemia.