Chemical Nature of Binding of Serotonin in the Central Nervous System

Abstract

BIOGENIC amines are mostly found in bound form in tissues, but little is known regarding the chemical nature of the bonds involved in the attachment of biogenic amines or their derivatives to macromolecules. We have studied certain aspects of the firm attachment of indoleamines or their derivatives to acid insoluble material (lipoproteins ?) obtained from the central nervous system. In those in vitro studies it was demonstrated that a large part of this incorporation occurs after conversion of the indoleamines to their corresponding aldehydes and can be prevented by the presence of pargyline (a monoamine oxidase inhibitor) in the medium^1,2. A similar type of incorporation of radioactivity into acid insoluble material was also observed after in vivo endocranial administration of labelled serotonin into mice³. Within a range of dosages (25 to 250 nmoles/g wet brain) this in vivo incorporation diminishes by pretreatment of the animal with monoamine oxidase inhibitors (MAOI)⁴. In the same dosage range 5-hydroxy-indole-3-acetaldehyde produces in rabbits characteristic changes of photic evoked responses of the optic cortex when injected intraventricularly⁵. When administered intraperitoneally at relatively higher dosages into newly hatched male chicks this aldehyde, like serotonin, induces eyelid closure and a depression in posture resembling true sleep⁵. At much lower dosages (5–10 nmoles/g brain), however, the effectiveness of MAOI pretreatment in preventing the in vivo incorporation of exogenously administered labelled serotonin rapidly diminishes. This is probably because at such small dosages the amount of exogenous amine which eventually enters the cells may be accommodated within the storage apparatus of the cells before it has the chance to be attacked by (mitochondrial) monoamine oxidase.