Effect of Noradrenaline on Phosphatase Activity in Synaptic Membrane of the Rat Brain

Abstract

THE classical experiments of Loewi¹ demonstrated the transmitter substance of the sympathetic nervous system to be adrenaline or noradrenaline^2,3. Several further investigations have shown a transmitter substance to be present in the central nervous system (CNS), that is, the hypothalamus, the central grey matter of mesencephalon and the area postrema^4,7. Differential centrifugation of a CNS homogenate has demonstrated the presence of noradrenaline in the synaptic vesicles of the synaptic junction^8–10. Electrophysiological investigation has revealed that electrical stimulation of amygdala or of terminals of bulbo-spinal neurones leads, in both instances, to a reduction of the noradrenaline content of certain areas of the brain^11–13. The molecular basis for the action of noradrenaline in the CNS is, however, unknown. Previous investigations of the pharmacological action of noradrenaline, particularly on different enzyme systems^14–16, have not provided the experimental evidence basic to a theoretical understanding of physiological events of depolarization and repolarization. The relationship of changes in the ion-flux across the synaptic membrane to the action of a transmitter substance has not been denned. Investigation (our report in preparation) of the distribution of phospholipids and glycolipids free from sialic acid in the sub-cellular fractions of hypothalamus revealed a preponderance of phosphatidyl-serine in the sub-mitochondrial fraction B–C¹⁹ using the method of De Robertis et al.^8,9. This discovery stimulated us to search for a possible function of phosphatidyl-serine in the synaptic endings. In vitro investigations revealed phosphatidyl-serine to be the only major lipid among phospholipids or glycolipids free from sialic acid of the CNS which binds the noradrenaline¹⁷.