Modification of cardiac adrenergic receptors by oxygen free radicals.
To examine the effects of oxygen free radicals on alpha- and beta-adrenergic receptors, rat heart crude membranes were incubated with xanthine plus xanthine oxidase, H2O2, or H2O2 plus Fe2+. The assay of beta-adrenergic receptors involving [3H]dihydroalprenolol (DHA) binding revealed that the maximal number of binding sites (Bmax) and dissociation constant (Kd) were increased by xanthine plus xanthine oxidase. H2O2 increased the Kd value for [3H]DHA binding. When a hydrophilic ligand, [3H]CGP-12177, was used for the beta-adrenergic receptor assay, an increase in Kd value without any changes in Bmax value was evident on treating the membranes with xanthine plus xanthine oxidase. The assay of alpha-adrenergic receptors involving [3H]prazosin binding showed a decrease in the number of binding sites and an increase in Kd value only after a prolonged period of incubation. Both H2O2 and H2O2 plus Fe2+ increased the Kd value for [3H]prazosin without changes in Bmax. Changes in both alpha- and beta-adrenergic receptors similar to those with crude membranes were also seen by employing the purified heart sarcolemmal membranes. These data indicate that adrenergic receptors in the sarcolemmal membranes are modified by oxygen free radicals.
Kaneko
M
M
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Chapman
D C
DC
Ganguly
P K
PK
Beamish
R E
RE
Dhalla
N S
NS
D000818:Animals; D004082:Dihydroalprenolol / Q000378:metabolism; D005609:Free Radicals; D006878:Hydroxides / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
D005609:Free Radicals; D006878:Hydroxides; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D010100:Oxygen; D011224:Prazosin