Paradoxical reversion of the inhibitory effects of dihydropyridine enantiomers on the calcium current in frog heart by CGP 28861.
A dihydropyridine CGP 28861 (5 x 10(-6) M) did not change slow inward Ca current as measured by the double sucrose gap method in frog atrial fibres but decreased the agonist effects of Bay K 8644, CGP 28392, (+)-(S)-202-791 and the antagonist effects of nifedipine and (+)-(PN)-200-110. Paradoxically, the weak antagonists (-)-(R)-202-791, (-)-(PN)-200-110 and (+)-Bay K 8644 increased Ca-current after washout of CGP 28861. These data suggest that CGP 28861 can convert the dihydropyridine Ca-channel receptor from an antagonistic site into an agonistic one.
Filippov
A
A
Institute of Biological Physics, USSR Acad. Sci., Pushchino, Moscow Region.
Kobrinsky
E
E
Porotikov
V
V
Saxon
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels; D004347:Drug Interactions; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011895:Rana ridibunda; D011978:Receptors, Nicotinic / Q000187:drug effects*
D015220:Calcium Channels; D011725:Pyridines; D011978:Receptors, Nicotinic; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; C058923:CGP 28861