DISTRIBUTION AND PROPERTIES OF CDP-DIGLYCERIDE:INOSITOL TRANSFERASE FROM BRAIN 1

CDP-diglyceride is converted to phosphatidyl inositol by several particulate subcellular fractions of guinea pig brain, with highest specific activity in the microsomal fraction. Optimal conditions with respect to pH, metal ion concentration, and substrate concentrations have been determined. The reaction was stimulated by the addition of bovine serum albumin and by Tween 80. Of several dl-CDP-diglycerides synthesized and used as substrates in a spectrophoto-metric assay for the enzyme, dl-CDP-didecanoin was the most active. The enzyme showed a high selectivity for myo-inositol. Of a number of compounds tested, only scyllo -inosose and epi -inosose served as substrates. Three inositol isomers and three myo -inositol monophosphates inhibited the reaction slightly. The most potent inhibitor found was galactinol, a myo -inositol galactoside.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66197/1/j.1471-4159.1969.tb06850.x.pd

Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66228/1/j.1471-4159.1987.tb05618.x.pd

Formation and inactivation of endogenous cannabinoid anandamide in central neurons

Anandamide (N-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phosphodiesterase-mediated cleavage of a novel phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger