The interaction of [3H]PY 108-068 and of [3H]PN 200-110 with calcium channel binding sites in rat brain

The binding properties of the tritiated calcium channel antagonists PY 108-069 and PN 200-110 were investigated in membrane fractions from rat brain in vitro. Both ligands reversibly interact with one apparent population of stereoselective binding sites which have pharmacological properties described for calcium channel binding sites. In a calcium buffer enhancement of [3H]PY 108-068 binding is observed with an EC50 at pCa 6.28 [3H]PN 200-110 binding is less sensitive to allosteric stimulation by diltiazem and to allosteric inhibition by verapamil and D 600 than [3H]PY 108-068 binding, suggesting that the former ligand may stabilize a high affinity configuration of the binding sites. After i.v. administration of [3H]PY 108-068 in vivo binding to membranes is observed in brain and heart, which, in contrast to total tissue radioactvity is sensitive to inhibtion by unlabelled (+)PN 200-110. These observations suggest that PY 108-068 can interact with its binding sites also in vivo. The results of ex vivo binding studies in brain and heart with [3H]PY 108-068 confirm and extend these observations. It could be shown that all investigated 1, 4-dihydropyridines (PY 108-068, PN 200-110, nifedipine, Bay K 8644) after i.p. administration can readily enter brain and heart tissue. (Author)