Chemical modification of the dihydropyridines binding sites by lysine reagent, pyridoxal 5’-phosphate

Treatment of rabbit brain membranes of the DHP binding sites of L-type Ca2+ channel with lysine-specific reagent resulted in a time-and concentration-dependent loss of [H-3]nitrendipine binding activity. Following exposure to the maximum concentration of PLP (100 mM), [H-3]nitrendipine binding was inhibited by up to 96.5%. Scatchard analysis of the binding data indicated that treatment with PLP resulted in a loss of [H-3]nitrendipine binding sites with no effect on binding affinity. Considerable protection against PLP inactivation was obtained by nifedipine. These results indicate that lysine residue plays a critical role in maintaining the DHP-binding sites in a conformation capable of ligand binding. (C) 1998 Elsevier Science Ltd. All rights reserved.