Do ethoxy radicals reduce 3H-nitrendipine binding in rat cardiac membranes?
The incubation of xanthine-oxidase (XOD) with rat cardiac membranes induced the formation of free radicals; they were identified by electron spin resonance spectroscopy (ESR) studies using 0.1 M 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) for spin-trapping. The following DMPO adducts were measured: DMPO-OH, which was produced during the first minute of incubation, DMPO-R radicals, which were present after 4 min of incubation and where the signal intensity remained constant for at least 20 min. The binding studies performed after 15 min incubation showed that XOD (1-50 mU) dose dependently reduced 3H-nitrendipine binding. This reduction was caused by a decrease in the density of binding sites while the affinity remained unchanged. These results suggest that ethoxy radical formation may be an important step in the regulation of L type calcium channels.
Matucci
R
R
Dip. Farmacologia Preclinica e Clinica, Università di Firenze, Italia.
Ottaviani
M F
MF
Campana
S
S
Bianchi
B
B
Bennardini
F
F
Moneti
G
G
Giotti
A
A
Franconi
F
F
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006321:Heart / Q000187:drug effects; D008024:Ligands; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D014969:Xanthine Oxidase / Q000494:pharmacology*
D003497:Cyclic N-Oxides; D005609:Free Radicals; D008024:Ligands; D013113:Spin Labels; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D009568:Nitrendipine; D014969:Xanthine Oxidase