Evidence for receptor and G-protein regulation of a phosphatidylethanolamine-hydrolysing phospholipase A1 in guinea-pig heart microsomes: stimulation of phospholipase A1 activity by DL-isoprenaline and guanine nucleotides.
While evidence has been presented for the receptor-mediated activation of phospholipases A2, C and D, the activation of phospholipase A1 subsequent to receptor activation has not been established. Phospholipase A1-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 substrate. 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 A1. GDP[S] inhibited the isoprenaline-mediated stimulation of phospholipase A1 activity. Phospholipase A1 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 A1 activity in guinea-pig heart microsomes is activated by the binding of isoprenaline to beta 2-adrenergic receptors. Furthermore the stimulation of phospholipase A1 activity by the agonist may be mediated via activation of G-proteins.
Badiani
K
K
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Arthur
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology*; D008861:Microsomes / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054466:Phospholipases A1; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D006150:Guanine Nucleotides; D010714:Phosphatidylethanolamines; D011943:Receptors, Adrenergic, beta; D002078:Butoxamine; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011433:Propranolol; D010741:Phospholipases A; D054466:Phospholipases A1; D019204:GTP-Binding Proteins; D007545:Isoproterenol