Interaction of dihydropyridine calcium channel agonists and antagonists with adenosine receptors.
We have confirmed our previous (Fredholm et al. 1986a) finding that the dihydropyridine calcium channel agonist Bay K 8644 can displace [3H]-R-PIA from its binding site, the adenosine A1-receptor. Bay K 8644 had an apparent Ki of 5.2 X 10(-6) M. The effect was shared by the two dihydropyridine calcium channel antagonists nifedipine and felodipine (Ki 4.2 and 8.7 X 10(-6) M, respectively). By contrast, two non-dihydropyridine calcium channel antagonists, verapamil and diltiazem, did not affect binding. Bay K 8644 displaced [3H]-R-PIA from its binding sites in a solubilized preparation. [3H]-XAC, a novel, potent A1-receptor antagonist ligand, was also displaced by the dihydropyridine compounds with a similar or slightly higher potency as the displacement of R-PIA. This suggests a direct interaction with the adenosine receptor rather than an effect on regulatory GTP-binding proteins. However, at 1 mumol/l neither Bay K 8644 nor nifedipine significantly attenuated cyclic AMP accumulation in rat hippocampi or the R-PIA-mediated adenylate cyclase inhibition. The results show that dihydropyridine compounds that act as agonists or antagonists on L-type calcium channels can also affect adenosine receptors. The potency of the compounds for this effect is much lower than their potency as calcium channel agonists or antagonists. The results may therefore be of more experimental than clinical significance.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010660:Phenylisopropyladenosine / Q000378:metabolism; D058914:Purinergic Antagonists; D011869:Radioligand Assay; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D002121:Calcium Channel Blockers; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014970:Xanthines; D010660:Phenylisopropyladenosine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C049140:1,3-dipropyl-8-phenylxanthine; D000242:Cyclic AMP