DIETARY LINOLEIC ACID-INDUCED CHANGES IN RESPIRATORY BETA-ADRENERGIC-RECEPTOR FUNCTION AND THE FORM OF ARRHENIUS PLOTS OF ISOPRENALINE-STIMULATED AND PROSTAGLANDIN-E(2)-STIMULATED ADENYLATE-CYCLASE ACTIVITY INA MODEL FOR ATOPY

Varying dietary linoleic acid altered lung membrane fatty acid composi te with linoleic acid content increasing from similar to 6% total in t hose on 3 en% diet to similar 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 similar to 26% t o similar to 19% total. Administration of Haemophilus influenzae, to a nimals on 6 en% linoleic acid, serving as a model for atopy, affected a small increase in the levels of 22.5 (n-3) and doubled those of 22.6 (n-3). beta-Adrenergic-induced tracheal relaxation and stimulation of lung adenylate cyclase were elevated by increasing dietary linoleic a cid from 3 to 6 en%, although such differences were abolished in the a topic model and when dietary linoleic acid was increased to 12 en%. Ar rhenius plots of NaF-stimulated lung adenylate cyclase activities exhi bited a break (t(1)) at similar to 26 degrees C in all dietary groups with unchanged activation energies and activity. In contrast, whilst b oth isoprenaline and PGE(2)-stimulated adenylate cyclase activities sh owed similar break-points in their Arrhenius plots, dietary linoleic a cid manipulation markedly altered their form. As with NaF-stimulated a ctivities then, irrespective of dietary manipulation and induction of atopy, these plots showed an invariant break occurring at similar to 2 6 degrees C. But, for animals on 3 and 6 en% diets, a second break was apparent at similar to 15 degrees C, which was slightly decreased to similar to 12 degrees C upon induction of atopy and completely abolish ed on increasing dietary linoleic acid to 12 en%. Accompanying such ch anges 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 select ively perturb adenylate cyclase activity when it is receptor-stimulate d by not when it is activated by direct G-protein stimulation with NaF . We suggest that atopy and dietary challenge elicit an asymmetric per turbation of the plasma membrane that predominantly affects the outer half of the lipid bilayer.