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 [3H]nitrendipine binding activity. Following exposure to the maximum concentration of PLP (100 mM), [3H]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 [3H]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.
Costa
B
B
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università degli Studi di Pisa, Italy.
Giusti
L
L
Martini
C
C
Lucacchini
A
A
D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000378:metabolism*; D004095:Dihydropyridines / Q000378:metabolism*; D007202:Indicators and Reagents; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000378:metabolism*; D011817:Rabbits
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007202:Indicators and Reagents; D011732:Pyridoxal Phosphate; D009568:Nitrendipine; D008239:Lysine