Carbachol-stimulated release of arachidonic acid and eicosanoids from brain cortex synaptoneurosome lipids of adult and aged rats.
Synaptoneurosomes from the brain cortex of adult rats (4 months old) and aged rats (27 months old), prelabeled with [14C]arachidonic acid (AA), were used as the source of enzyme(s) and substrates to study the effect of a cholinergic agonist on the release of AA and eicosanoids. In synaptoneurosomes from adult brains, carbachol, the nonhydrolyzable analog of acetylcholine, increased AA release by 16% in the presence of 2 mM calcium. This agonist-mediated AA release occurred specifically from phosphatidylinositol (PI). Concomitantly, carbachol in the presence of 2 mM Ca2+ significantly activated the formation of 15-HETE and PGF2 alpha. This effect of carbachol on the level of eicosanoids was also observed in the presence of endogenous calcium. In synaptoneurosomes from aged brains, carbachol had no effect on the release of AA and eicosanoids. The results of studies involving inhibitors of phospholipase A2 (PLA2) and phospholipase C (PLC) suggested that PLA2 is almost completely responsible for the Ca(2+)-dependent, carbachol-mediated AA liberation. The distribution of labeled AA in the lipids after incubation of synaptoneurosomes in the presence of 2 Mm Ca2+ and carbachol indicated that in aged synaptoneurosomes, the muscarinic receptor-mediated degradation of phosphoinositides through phospholipase C is preserved, but the turnover of the phosphoinositide cycle is probably suppressed. These results indicate that aging significantly affects the population of cholinergic-muscarinic receptors coupled to PLA2.
Strosznajder
J
J
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
Samochocki
M
M
D000375:Aging / Q000502:physiology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D015777:Eicosanoids; D011976:Receptors, Muscarinic; D016718:Arachidonic Acid; D002217:Carbachol; D010741:Phospholipases A; D054467:Phospholipases A2