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 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.