Evidence for receptor and G-protein regulation of a phosphatidylethanolamine-hydrolysing phospholipase A(1) in guinea-pig heart microsomes: Stimulation of phospholipase A(1) activity by DL-isoprenaline and guanine nucleotides

While evidence has been presented for the receptor-mediated activation of phospholipases A(2), C and D, the activation of phospholipase A(1) subsequent to receptor activation has not been established. Phospholipase A(1)-catalysed hydrolysis of 1-palmitoyl-2-linoleoyl-glycerophosphoethanolamine (GPE) by guinea-pig heart microsomes was stimulated 40-60 % by isoprenaline. This isoprenaline-mediated increase in activity was blocked by propranolol and butoxamine, a specific beta(2)-adrenergic antagonist, but not by atenolol, a specific beta(1)-adrenergic antagonist. Neither clonidine nor phenylephrine, alpha(1)- and alpha(2)- adrenergic agonists respectively, had a stimulatory effect on the hydrolysis of the PE sub strate. Guanosine 5'-[gamma-thio] triphosphate (GTP[S]) and guanosine 5'-[beta,gamma-imido]triphosphate, but not guanosine 5'-[beta-thio]diphosphate (GDP[S]) or adenosine 5'-[gamma-thio]triphosphate, stimulated the hydrolysis of 1-palmitoyl-2-linoleoyl-GPE by phospholipase A(1). GDP[S] inhibited the isoprenaline-mediated stimulation of phospholipase A(1) activity. Phospholipase A(1) hydrolysis of 1-palmitoyl-2-linoleoyl-GPE was not dependent on cations; however, the stimulatory effects of isoprenaline and GTP[S] on the hydrolytic activity were abolished by cation chelators. The above data suggest that phospholipase A(1) activity in guinea-pig heart microsomes is activated by the binding of isoprenaline to beta(2)-adrenergic receptors. Furthermore the stimulation of phospholipase A(1) activity by the agonist may be mediated via activation of G-proteins.