Uptake of adenosine and release of adenine derivatives in mammalian non-myelinated nerve fibres at rest and during activity.

1. Influx of adenosine into rabbit non-myelinated nerve fibres was measured using [2-(3)H]adenosine. The uptake of radioactivity increased linearly with duration of incubation for up to 60 min and adenosine concentration up to 200 mum. The uptake at different adenosine concentrations showed a saturable component with a half-maximal activation at 17.1 mum and a linear part.2. The radioactivity taken up was rapidly incorporated into AMP, ADP and ATP. Isotopic equilibrium between the nucleotides was achieved within 15 min.3. The uptake of (3)H from 0.2 mum-adenosine was almost completely inhibited by addition of 200 mum-adenosine and to a similar extent by 200 mum-tubercidin and AMP; a 70% inhibition was found with ATP and ADP; alpha, beta methylene-ADP had no effect.4. ATP, ADP and AMP added to the extracellular medium of a desheathed vagus were slowly hydrolysed.5. In preparations loaded with [2-(3)H]adenosine and then washed with adenosine and label-free solution there was a steady efflux of radioactivity amounting to 0.18 x 10(-3)/min. Addition of adenosine or tubercidin transiently increased the efflux.6. Electrical stimulation caused an extra release of radioactivity. The extra fractional loss was 21.8 x 10(-6)/impulse in preparations that had rested for several hours; it decreased to 2.3 x 10(-6)/impulse when stimulation was applied after a 30 min rest.7. The radioactivity of the resting efflux and of the extra efflux after stimulation was found mostly in inosine and hypoxanthine; adenosine and adenine accounted for only 3%, and the nucleotides for less than 1% of the efflux.8. Adenosine added to the external medium of a desheathed nerve was slowly deaminated.9. It is concluded that inosine and hypoxanthine found in the effluent from desheathed vagus nerve trunk result from release of these compounds from nerve fibres and not from extracellular breakdown of released ATP or adenosine.10. Electrical activity in non-myelinated nerve fibres of the nerve trunk thus causes the release of metabolites (inosine and hypoxanthine) together with small amounts of adenosine and adenine, while release of ATP and other nucleotides is almost completely absent.