High affinity specific [3H](+)PN 200-110 binding to dihydropyridine receptors associated with calcium channels in rat cerebral cortex and heart.
The binding properties of the 1,4-dihydropyridine calcium channel antagonist, [3H](+)PN 200-110, were studied in rat cerebral cortical and cardiac homogenates (37 degrees C, Krebs phosphate buffer). Specific binding of [3H](+)PN 200-110 was saturable, reversible, and of high affinity (Kd values are 35 and 64 pM for the cerebral cortex and heart, respectively). In parallel studies with [3H](+)PN 200-110, the dissociation constant of [3H]nitrendipine was 10-12 times higher. Substituted dihydropyridine calcium channel antagonists and agonists competitively inhibited specific [3H](+)PN 200-110 binding, but d-cis diltiazem enhanced and verapamil incompletely inhibited [3H](+)PN 200-110 binding in both the cerebral cortex and the heart. The effects of diltiazem and verapamil on [3H](+)PN 200-110 binding were due mainly to alterations in the dissociation constant (Kd), without alterations in the binding density (Bmax). The new [3H](+)PN 200-110 receptor binding assay is remarkable for its low degree of nonspecific binding as compared to [3H]nitrendipine at physiological temperatures. [3H](+)PN 200-110 is a useful ligand for the further analysis of the dihydropyridine binding sites associated with calcium channels.
D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels; D002540:Cerebral Cortex / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D017275:Isradipine; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D010069:Oxadiazoles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium; D017275:Isradipine