Flurbiprofen,A Cyclooxygenase Inhibitor,Reduces the Brain Arachidonic Acid Signal in Response to the Cholinergic Muscarinic Agonist,Arecoline, in Awake Rats |
| |
Authors: | Mireille Basselin Nelly E. Villacreses Ho-Joo Lee Jane M. Bell Stanley I. Rapoport |
| |
Affiliation: | (1) Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bldg 9, Room 1S126, MSC 0947, 9 Memorial Drive, Bethesda, MD 20892, USA |
| |
Abstract: | Cholinergic muscarinic receptors, when stimulated by arecoline, can activate cytosolic phospholipase A2 (cPLA2) to release arachidonic acid (AA) from membrane phospholipid. This signal can be imaged in the brain in vivo using quantitative autoradiography following the intravenous injection of radiolabeled AA, as an increment in a regional brain AA incorporation coefficient k*. Arecoline increases k* significantly in brain regions having muscarinic M1,3,5 receptors in wild-type but not in cyclooxygenase (COX)-2 knockout mice. To further clarify the roles of COX enzymes in the AA signal, in this paper we imaged k* following arecoline (5 mg/kg i.p.) or saline in each of 81 brain regions of unanesthetized rats pretreated 6 h earlier with the non-selective COX inhibitor flurbiprofen (FB, 60 mg/kg s.c.) or with vehicle. Baseline values of k* were unaffected by FB treatment, which however reduced by 80% baseline brain concentrations of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), eicosanoids preferentially derived from AA via COX-2 and COX-1, respectively. In vehicle-pretreated rats, arecoline increased the brain PGE2 but not TXB2 concentration, as well as values for k* in 77 of the 81 brain regions. FB-pretreatment prevented these arecoline-provoked changes. These results and those reported in COX-2 knockout mice suggest that the AA released in brain following muscarinic receptor-mediated activation is lost via COX-2 to PGE2 but not via COX-1 to TXB2, and that increments in k* following arecoline largely represent replacement by unesterified plasma AA of this loss. |
| |
Keywords: | Arachidonic acid Cyclooxygenase Flurbiprofen Muscarinic receptors Cytosolic phospholipase A2 Prostaglandin E2 Thromboxane B2 COX-1 COX-2 NSAID |
本文献已被 PubMed SpringerLink 等数据库收录! |
|