Purine Metabolite Inosine is an Adrenergic Neurotrophic Substance for Cultured Chicken Sympathetic Neurons

Purines are ubiquitous endogenous cellular metabolites that have been postulated as neurotransmitters or neuromodulators in the nervous system. Recently, we showed that a low-molecular-mass component present in liver-conditioned medium selectively enhances the adrenergic properties of dissociated ch...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1988-11, Vol.85 (21), p.8301-8305
Main Authors: Zurn, Anne D., Do, Kim Quang
Format: Article
Language:English
Subjects:
Absorption spectra
Adrenergics
Animals
Biological and medical sciences
Brain
Catecholamines
Cell physiology
Cells, Cultured
Cellular metabolism
Chick Embryo
Chromatography
Chromatography, High Pressure Liquid
Dipyridamole - pharmacology
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
Inosine - metabolism
Leucine - metabolism
Molecular and cellular biology
Nervous system
Neurons
Neurons - metabolism
Neuroscience
Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ
Purines
Responses to growth factors, tumor promotors, other factors
Sympathetic Nervous System - cytology
Sympathetic Nervous System - metabolism
Theophylline - pharmacology
Vertebrates: nervous system and sense organs
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Summary:Purines are ubiquitous endogenous cellular metabolites that have been postulated as neurotransmitters or neuromodulators in the nervous system. Recently, we showed that a low-molecular-mass component present in liver-conditioned medium selectively enhances the adrenergic properties of dissociated chicken sympathetic neurons in culture. We report here that this substance is inosine, a purine metabolite. Indeed, analysis of the low-molecular-mass fraction of liver-conditioned medium by HPLC shows that the neurotrophic activity coelutes with and has the same absorption spectrum as inosine. Inosine increases incorporation of [3H]leucine into neuronal protein and stimulates catecholamine, but not acetylcholine, production by the sympathetic neurons in a dose-dependent fashion (half-maximal stimulation at 10-6 M). This effect can be blocked by 5 × 10-6 M dipyridamole, an inhibitor of nucleoside transport. Inosine therefore appears to be capable of modulating adrenergic phenotypic expression in cultured sympathetic neurons by acting via an as-yet-unknown intracellular pathway.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.21.8301