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Stimulation of Phospholipase A 2 and Secretion of Catecholamines from Brain Synaptosomes by Potassium and A23187
Author(s) -
Bradford Peter G.,
Marinetti Guido V.,
Abood Leo G.
Publication year - 1983
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1983.tb00881.x
Subject(s) - lysophosphatidylcholine , chemistry , synaptosome , arachidonic acid , lysophosphatidylethanolamine , medicine , endocrinology , depolarization , stimulation , phospholipase a2 , potassium , phospholipase , phosphatidylcholine , biochemistry , phospholipid , biology , enzyme , in vitro , membrane , organic chemistry
Potassium depolarization of rat brain synaptosomes (containing incorporated l‐acyl‐2‐[ 14 C]arachidonyl‐phosphatidylcholine) stimulated endogenous phospholipase A 1 (EC 3.1.1.32) and A 2 (EC 3.1.1.4), as determined by the formation of [ 14 C]lysophosphatidylcholine, [ 14 C]arachidonate, and [ 14 C]prostaglandins, and also stimulated the secretion of [ 3 H]catecholamines. The phospholipase A 2 stimulation, dependent on calcium, was elicited in resting synaptosomes by A23187 and was demonstrated with incorporated 1‐acyl‐2‐[ l4 C]oleoyl‐phosphatidylcholine but not with incorporated [ I4 C]phosphatidylethanolamine or [ l4 C]phosphatidylserine. Inhibitors of phospholipase A 2 [ p ‐bromophenacylbromide (10 μ M ), trifluoperazine (3 μ M ), and quinacrine (3 μ M ) reduced the potassium‐stimulated [ 3 H]catecholamine release from synaptosomes to 78, 39. and 55%, respectively, of depolarized controls. The addition of lysophosphatidylcholine increased the release of [ 3 H]norepinephrine to levels observed with potassium depolarization, whereas lysophosphatidylethanolamine, lysophosphatidylserine, and sodium dodecyl sulfate were much less effective. Potassium stimulation of synaptosomes increased the endogenous levels of free arachidonic acid and prostaglandins E 2 and F 2α . Indomethacin and aspirin decreased the amounts of prostaglandins formed, allowed the accumulation of free arachidonic acid, and diminished the potassium‐stimulated release of [ 3 H]dopamine. p ‐Bromophenacylbromide inhibited the formation of prostaglandin F 2α . Addition of prostaglandin E 2 inhibited, whereas prostaglandin F 2α enhanced the release of [ 3 H]norepinephrine. These results suggest that calcium influx induced by synaptosomal depolarization activates endogenous phospholipase A 2 , with subsequent formation of lysophosphatidylcholine and prostaglandins, both of which may modulate neurosecretion.