title: Purine metabolite inosine is an adrenergic neurotrophic substance for cultured chicken sympathetic neurons.
abstract: 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 x 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.
authors.affiliation: Department of Biochemistry, Sciences II, Geneva, Switzerland.
authors.forename: A D
authors.initials: AD
authors.lastname: Zurn
authors.forename: K Q
authors.initials: KQ
authors.lastname: Do
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002851:Chromatography, High Pressure Liquid; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007288:Inosine / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology
chemical_list: D007288:Inosine; D004176:Dipyridamole; D013806:Theophylline; D007930:Leucine