The effect of hydrogen peroxide on beta-adrenoceptor function in the heart.
A membrane preparation of calf heart left ventricle has been used to study the effect of radical stress on the beta-adrenoceptor complex. To this end the membranes were incubated for 30 minutes with several concentrations of hydrogen peroxide. This resulted in a dose dependent peroxidation of the membrane lipids. Preincubation with hydrogen peroxide in the concentration range 10(-7)-10(-3) M caused an increase in specific (-)-[125I]-Iodocyanopindolol binding, possibly due to a decrease in membrane fluidity as a result of lipid peroxidation, thus making the receptor protein more accessible. Higher concentrations H2O2 reduced the specific (-)-[125I]-Iodocyanopindolol binding, which is most likely the effect of deterioration of the receptor protein by the more pronounced radical stress induced by these higher concentrations. Also adenylate cyclase activity was affected by radical stress. Basal cyclic-AMP production and cyclic-AMP production induced by NaF (10(-2) M) or guanylylimidodiphosphate (10(-4) M), was suppressed after pretreatment with concentrations of H2O2 above 10(-4) M. This indicates a higher sensitivity of the adenylate cyclase toward radical stress when compared to the receptor protein. Our results show that radical stress can perturb beta-adrenoceptor function considerably in the heart.
Haenen
G R
GR
Department of Pharmacochemistry, Subfaculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Van Dansik
P
P
Vermeulen
N P
NP
Timmerman
H
H
Bast
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002417:Cattle; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D006861:Hydrogen Peroxide; D000262:Adenylyl Cyclases