Dietary linoleic acid-induced changes in respiratory β-adrenergic receptor function and the form of arrhenius plots of isoprenaline- and prostaglandin E2-stimulated adenylate cyclase activity in a model for atopy

Abstract Varying dietary linoleic acid altered lung membrane fatty acid composition with linoleic acid content increasing from ∼6% total in those on 3 en% die to ∼14% total fatty acid in those on a 12 en% diet. Accompanying this were two- to three-fold increases in the levels of the elongation products of linoleic acid, namely 20:2 (n-6) and 22:5 (n-6) and a decrease in 18:1 oleic acid from ∼26% to ∼19% total. Administration of Haemophilus influenzae , to animals on 6 en% linoleic acid, serving as a model for atopy, effected a small increases in the levels of 22:5 (n-3) and doubled those of 22:6 (n-3). β-Adrenergic-induced tracheal relaxation and stimulation of lung adenylate cyclase were elevated by increasing dietary linoleic acid from 3 to 6 en%, although such differences were abolished in the atopic model and when dietary linoliec acid was increased to 12 en%. Arrhenius plots of NaF-stimulated lung adenylate cyclase activities exhibited a break (t 1 ) at ∼26°C in all dietary groups with unchanged activation energies and activity. In contrast, whilts both isoprenaline and PGE 2 -stimulated adenylate cyclase activities showed similar break-points in their Arrhenius plots, dietary linoleic acid manipulation markedly altered their form. As with NaF-stimulated activities then, irrespective of dietary manipulation and induction of atopy, these plots showed an invariant break occurring at ∼26°C. But, for animals on 3 and 6 en% diets, a second break was apparent at ∼15°, which was slightly decreased to ∼12°C upon induction of atopy and completely abolished on increasing dietary linoleic acid to 12 en%. Accompanying such changes were marked alterations in activation energies. We suggest that profound changes in lung plasma membrane bilayer properties occur upon both altering dietary linoleic acid levels and in atopy. These selectively perturb adenylate cyclase activity when it is receptor-stimulated but not when it is activated by direct G-protein stimulation with NaF. We suggest that atopy and dietary challenge elicit an asymmetric perturbation of the plasma membrane that predominantly affects the outer half of the lipid bilayer.