AUGMENTATION OF CYCLIC-AMP CONTENT INDUCED BY LYSOPHOSPHATIDYL CHOLINE IN RABBIT HEARTS

Summary: The accumulation of both lysophosphoglycerides and cyclic AMP in ischaemic myocardium has been associated with electrophysiological deterioration of the heart. Although the increase in concentration of cyclic AMP is mediated in part by adrenergic stimulation, some of the increase occurs despite β-adrenergic blockade. Thus, we considered the possibility that lysophosphoglycerides may contribute to the increases in myocardial cyclic AMP in ischaemic zones by stimulating adenylate cyclase. Accordingly, we examined the effects of albumin-bound lysophosphatidyl choline in concentrations simulating those in extracts of ischaemic myocardium on adenylate cyclase and phosphodiesterase activities in rabbit and cat myocardial broken cell preparations and on cyclic AMP content of isolated perfused rabbit hearts. Lysophosphatidyl choline (0.4 to 1.2 mmol·litre-1) augmented basal activity of adenylate cyclase by approximately 30% in broken cell preparations without affecting phosphodiesterase activity. Lysophosphatidyl choline (1 and 2 mmol·litre-1) did not alter isoprenaline-stimulated activity but reduced fluoride-stimulated activity by 31 and 39% of values obtained in the absence of lysophosphatidyl choline. In isolated perfused hearts from normal rabbits and those pretreated with reserpine to deplete the heart of catecholamines, lysophosphatidyl choline (2 mmol·litre-1) augmented the concentration of cyclic AMP from 4.6 ± 0.3 to 11.4 ± 1.3 pmol·mg protein-1 (P <0.005) and from 4.9 ± .4 to 8.0 ± .4 pmol·mg protein-1 (P <0.005) respectively. Thus, accumulation of lysophosphatidyl choline during ischaemia could contribute to the transiently increased concentration of cyclic AMP seen typically in ischaemic myocardium.