Role of serine esterase in A23187-mediated activation of phospholipase A2 in pulmonary endothelium.
To test the hypothesis that an endothelial cell membrane-associated serine esterase is involved in regulating phospholipase A2 (PLA2), we studied the effect of the calcium ionophore A23187 on intracellular PLA2 activity and arachidonic acid (AA) release in bovine pulmonary arterial endothelial cells. Exposure of these cells to A23187 causes a concentration-dependent increase in PLA2 activity and [14C]AA release. In addition to increasing PLA2 activity and AA release, A23187 enhances the activity of endothelial cell membrane-associated serine esterase that acts on the synthetic substrate N alpha-p-tosyl-L-arginine methyl ester. Serine esterase inhibitors, such as phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate, prevent the A23187-mediated increase in serine esterase activity, PLA2 activity, and AA release. Pretreatment of the cells with actinomycin D or cycloheximide does not prevent the A23187-mediated increase in AA release, serine esterase activity, or PLA2 activity. The membrane-associated serine esterase activity directly correlates with membrane PLA2 activity. These results suggest that a membrane-associated serine esterase plays a pivotal role in regulating PLA2 activity after exposure to A23187.
Chakraborti
S
S
Department of Biochemistry and Biophysics, University of Kalyani, India.
Michael
J R
JR
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation; D004950:Esterases / Q000037:antagonists & inhibitors / Q000502:physiology*; D007531:Isoflurophate / Q000494:pharmacology; D009994:Osmolar Concentration; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011651:Pulmonary Artery / Q000166:cytology / Q000201:enzymology*
D007531:Isoflurophate; D016718:Arachidonic Acid; D000001:Calcimycin; D010664:Phenylmethylsulfonyl Fluoride; D004950:Esterases; C022635:serine esterase; D010741:Phospholipases A; D054467:Phospholipases A2