CYTOSOLIC PHOSPHOLIPASE-A2 (CPLA2) DISTRIBUTION IN MURINE BRAIN AND FUNCTIONAL-STUDIES INDICATE THAT CPLA2 DOES NOT PARTICIPATE IN MUSCARINIC RECEPTOR-MEDIATED SIGNALING IN NEURONS

Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of membrane phospholipids and has been suggested as an effector in the receptor-mediated release of arachidonic acid in signal transduction. The potential role of cPLA2 a s an effector in muscarinic acetylcholine receptor signaling was inves tigated through ectopic expression of either the mi or m5 receptor in combination with cPLA2 in COS-1, CHO and U-373 MG cell lines. U-373 MG and COS-1 cells express undetectable or very low levels of cPLA2. CHO cell extracts are characterized by a significant endogenous PLA2 acti vity that was increased over 20-fold following transient expression wi th cPLA2 cDNA. However, in none of the cells lines did the co-expressi on of muscarinic receptor and cPLA2 result in a significant increase i n muscarinic receptor-mediated arachidonic acid release over cells exp ressing muscarinic receptor alone. The distribution of cPLA2 mRNA and cPLA2 immunoreactivity in murine brain were determined in order to inv estigate a potential role for cPLA2 in neurotransmission. cPLA2 mRNA w as expressed in white matter, including cells contained within linear arrays characteristic of interfascicular oligodendrocytes. cPLA2 immun oreactivity in white matter was evident throughout the processes of fi brous astrocytes. cPLA2 expression in gray matter was confined to astr ocytes at the pial surface of the brain. cPLA2 mRNA was detected in pi a mater, both at the brain surface and inner core of the choroid plexu s. cPLA2 may not be directly linked to neurotransmission since enzyme expression, mRNA, and cPLA2 immunoreactivity were undetectable in neur ons of murine brain. Support or regulation of neurotransmission may be provided through the activity of cPLA2 in glial cells. (C) 1998 Elsev ier Science B.V. All rights reserved.