Resting and arecoline-stimulated brain metabolism and signaling involving arachidonic acid are altered in the cyclooxygenase-2 knockout mouse |
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Authors: | Basselin Mireille Villacreses Nelly E Langenbach Robert Ma Kaizong Bell Jane M Rapoport Stanley I |
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Institution: | Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA; National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA |
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Abstract: | Studies were performed to determine if cyclooxygenase (COX)-2 regulates muscarinic receptor-initiated signaling involving brain phospholipase A2 (PLA2) activation and arachidonic acid (AA; 20 : 4n-6) release. AA incorporation coefficients, k* (brain 1–14C]AA radioactivity/integrated plasma radioactivity), representing this signaling, were measured following the intravenous injection of 1–14C]AA using quantitative autoradiography, in each of 81 brain regions in unanesthetized COX-2 knockout (COX-2–/–) and wild-type (COX-2+/+) mice. Mice were administered arecoline (30 mg/kg i.p.), a non-specific muscarinic receptor agonist, or saline i.p. (baseline control). At baseline, COX-2–/– compared with COX-2+/+ mice had widespread and significant elevations of k*. Arecoline increased k* significantly in COX-2+/+ mice compared with saline controls in 72 of 81 brain regions, but had no significant effect on k* in any region in COX-2–/– mice. These findings, when related to net incorporation rates of AA from brain into plasma, demonstrate enhanced baseline brain metabolic loss of AA in COX-2–/– compared with COX-2+/+ mice, and an absence of a normal k* response to muscarinic receptor activation. This response likely reflects selective COX-2-mediated conversion of PLA2-released AA to prostanoids. |
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Keywords: | arachidonic acid arecoline brain cyclooxygenase-2 knockout muscarinic receptor phospholipase A2 |
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