Interaction of palmitoyl carnitine with calcium antagonists in myocytes.
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 Ca2+ channels, with calcium antagonists were investigated. 2. Bay K 8644 (1-100 nM) and palmitoyl carnitine (0.2-30 microM) 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 nM for Bay K 8644 and 2 microM for palmitoyl carnitine. Higher concentrations (20-30 microM) 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 microM but higher concentrations caused tachycardia followed by cessation of beating. High concentrations of both palmitoyl carnitine and LPC (100 microM) caused break-up of the aggregates, presumably as a result of detergent effects. 3. Palmitoyl carnitine (1-100 microM) reversed the inhibitory effects of nisoldipine (0.3 microM), diltiazem (10 microM) and verapamil (1 microM). 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 microM) or lidoflazine (7 microM); 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 Ca2 + channel may have clinical relevance for the use of calcium antagonists in ischaemia.
Patmore
L
L
Syntex Research Centre, Riccarton, Edinburgh.
Duncan
G P
GP
Spedding
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D002642:Chick Embryo; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D008244:Lysophosphatidylcholines; D010172:Palmitoylcarnitine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002331:Carnitine; D002118:Calcium