title: Manoalide, a phospholipase A2 inhibitor, inhibits arachidonate incorporation and turnover in brain phospholipids of the awake rat.
abstract: The Fatty Acid method was used to determine whether incorporation of plasma radiolabeled arachidonic acid into brain phospholipids is controlled by phospholipase A2. Awake rats received an i.v. injection of a phospholipase A2 inhibitor, manoalide (10 mg/kg), and then were infused i.v. with [1-(14)C]arachidonate or [3H]arachidonate. Animals were killed after infusion by microwave irradiation, and tracer distribution was analyzed in brain phospholipid, neutral lipid and acyl-CoA pools. Calcium-independent phospholipase A2 activity in brain homogenate was reduced by manoalide, whereas phospholipase C activity was unaffected. At 60 min but not at 20 or 40 min after its injection, manoalide had significantly decreased by 50% incorporation of unesterified arachidonate into and turnover within brain phospholipids, taking into account dilution of the brain arachidonoyl-CoA pool by recycled arachidonate. Manoalide also increased by 100% the net rate of unesterified arachidonate incorporation into brain triacylglycerol. This study indicates that manoalide can be used to inhibit brain phospholipase A2 in vivo, and that phospholipase A2 plays a critical role in arachidonate turnover in brain phospholipids and neutral lipids.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health Bethesda, Maryland 20892-1582, USA.
authors.forename: E
authors.initials: E
authors.lastname: Grange
authors.forename: O
authors.initials: O
authors.lastname: Rabin
authors.forename: J
authors.initials: J
authors.lastname: Bell
authors.forename: M C
authors.initials: MC
authors.lastname: Chang
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013729:Terpenes / Q000494:pharmacology*; D014851:Wakefulness
chemical_list: D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; D010743:Phospholipids; D013729:Terpenes; C026563:arachidonyl-coenzyme A; D016718:Arachidonic Acid; C045673:manoalide; D010741:Phospholipases A; D054467:Phospholipases A2