THE EFFECTS OF PHOSPHOLIPASE A_2 ON BETA ADRENOCEPTOR FUNCTION IN ISOLATED CARDIAC CELLS

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The role of phospholipids in the maintenance of β-adrenoceptor function was investigated in isolated canine myocytes prepared from eight adult mongrel dogs by using collagenase. The characteristics of β-adrenoceptors were assessed by determining the number and the affinity of receptors by a radio-active ligand binding assay using ^<125>I-iodocyanopindolol. The increase in cyclic AMP content induced by isoproterenol or forskolin was also determined by radioimmunoassay with or without pretreatment with phospholipase (PLase) A_2. The amount of free fatty acids released from isolated myocytes by PLase A_2 was measured by high-performance liquid chromatography. PLase induced a significant decrease in the number of β-adrenoceptors but did not affect their affinity. Although the isoproterenol-stimulated increase in cyclic AMP was significantly inhibited by the pretreatment with PLase A_2, the forskolin-stimulated increase as not affected. Responsive accumulation of cyclic AMP to isoproterenol was much more impaired than the decrease in β-adrenoceptor number. These results indicate that PLase A_2 deteriorates the function of the adenylate cyclase system linked-β-adrenoceptor, and suggest that PLase A_2 affects both β-adrenoceptors and the coupling of β-adrenoceptors with adenylate cyclase.
社団法人日本循環器学会の論文
1985-11-20