Characterization of a Dopaminergic Stimulatory Factor Derived from Monoclonal Cell Lines of Striatal Origin

摘要

A lysate of an immortalized monoclonal cell line derived from the striatum (X61) contains two types of chemically distinct factors which are capable of increasing the dopamine content of an immortalized, dopaminergic mouse mesencephalic cell line (MN9D). One type of factor could be extracted from the cell lysate by isoamyl alcohol/chloroform and was identified to be composed primarily of oleic acid. The other type of factor was water-soluble and consisted of ethanolamine and phosphoethanolamine. Our experimental results indicate that both types of dopaminergic stimulatory factors elevate the dopamine content of mesencephalic-derived MN9D cells through an increase in storage capacity, possibly via a membrane fusion mechanism, rather than by enhancing neurotransmitter synthesis. These findings suggest a novel mechanism of action by which such factors regulate the dopaminergic phenotype. Although developing, fetal primary dopaminergic neurons in reaggregate culture were not responsive to the dopaminergic stimulatory effect of ethanolamine, there remains the possibility that phospholipid precursor therapy may be of some utility in neurodegenerative disorders, such as Parkinson's disease, given the need of neurons to repair damaged cell membranes.