The effects of 4-hydroxy-2,3-trans-nonenal on beta-adrenoceptors of rat lung membranes.
Lung membranes are susceptible to oxygen radicals, formed during inflammation, redox cycling of toxic agents, exposition to ozon etc. Oxygen radicals may modify the beta-adrenergic response. However, at the same time beta-adrenoceptors of the lung are frequently addressed in therapy. We embarked upon this problem by studying the effects of the aldehyde 4-hydroxy-2,3-transnonenal (HNE), one of the major products of lipid peroxidation, on the density of beta-adrenoceptors of rat lung membranes. It is shown, that the physiological important sulfhydryl blocking agent HNE inactivates the beta-adrenoceptors in a time- and concentration dependent (0.5-2.5 mM) way, indicated by a decrease in (-)-[3H]dihydroalprenolol (DHA) binding to lung membranes. Moreover, it is shown that combined treatment of HNE with (-)-isoproterenol (0.5 microM) or 1-alprenolol (0.5-10 nM) does not influence the extent of inactivation of beta-adrenoceptors by HNE. This is in contrast with previous studies, conducted with other, synthetic, sulfhydryl blocking agents, such as N-ethylmaleimide (NEM), suggesting that an other mechanism of inactivation is involved upon HNE treatment.
D000447:Aldehydes / Q000494:pharmacology*; D000478:Alkylation; D000818:Animals; D004082:Dihydroalprenolol / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism
D000447:Aldehydes; D008054:Lipid Peroxides; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; C027576:4-hydroxy-2-nonenal; D007545:Isoproterenol