Carbon centered radicals reduce the density of L-type calcium channels in rat cardiac membranes.
The carbon centered radicals generated by preincubation of cumene hydroperoxide with rat cardiac membranes dose dependently reduced the Bmax of [3H]nitrendipine binding, while KD was unchanged. The reduction induced by cumene hydroperoxide was prevented by 2,6-di-t-butlyl-4-methyl-phenol. The generation of OH did not influence the [3H]nitrendipine binding; also other oxidative agents (H2O2 and HClO4) did not modify this binding. Therefore the reduction in [3H]nitrendipine binding sites is not attributable to generic oxidative stress but to the formation of carbon centered radicals.
Matucci
R
R
Department of Preclinical and Clinical Pharmacology, Cystic Fibrosis Center-Meyer Hospital, University of Florence, Italy.
Bianchi
B
B
Ottaviani
M F
MF
Campana
S
S
Bennardini
F
F
Franconi
F
F
D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010472:Perchlorates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D001555:Benzene Derivatives; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D005609:Free Radicals; D016877:Oxidants; D010472:Perchlorates; D017670:Sodium Compounds; D013481:Superoxides; D002084:Butylated Hydroxytoluene; C031068:sodium perchlorate; D009568:Nitrendipine; D006861:Hydrogen Peroxide; C007164:cumene hydroperoxide