Release of adenosine, inosine and hypoxanthine from rabbit non‐myelinated nerve fibres at rest and during activity.

Abstract

SUMMARY1. The composition of the efflux from desheathed rabbit vagus nerve, loaded with radioactivity by incubation in [3H]adenosine, was studied at rest and during electrical activity and after application of inhibitors of ecto-enzymes and modifications of intermediary metabolism. In addition, the degradation ofexternally applied ATP and adenosine was examined.2.[3H]ATP applied to the incubation medium was degraded to ADP, AMP, adenosine and inosine. The hydrolysis to nucleosides was inhibited by a, ,8-methylene ADP; the appearance of AMP and nucleosides was slowed by fi, y-methylene ATP.Deamination of [3H]adenosine was blocked by 2-deoxycoformycin. 3. The effluent from resting and stimulated preparations showed the presence of large amounts of inosine and hypoxanthine, smaller amounts of adenosine and adenine and traces of nucleotides. The composition of the effluent was not significantly altered by addition of a, fl-methylene ADP; fi, y-methylene ATP or 2-deoxycoformycin.4. Application of glucose-free solutions caused a large release of adenosine instead of inosine and hypoxanthine and a small increase in resting and stimulated efflux of 3H. Addition of 2-deoxyglucose produced a large increase in resting efflux and increased liberation of adenosine. Cyanide, 2, 4-dinitrophenol, arsenate or salicylate increased the resting efflux of adenosine, inosine and hypoxanthine, and the effect of activity.5. It is concluded that electrical activity leads to release of adenosine, inosine and hypoxanthine, in various proportions depending on metabolic state, and that there is practically no liberation of nucleotides from nerve axons.

Association of the ecto‐ATPase NTPDase2 with glial cells of the peripheral nervous system

“…The identity of the ATP-hydrolyzing enzyme associated with myelinating Schwann cells is unclear, but a possible candidate is NTPDase3. Interestingly, an extracellular hydrolysis of ATP to ADP, AMP, and adenosine has been observed early on in the nonmyelinated fibers of the desheathed rabbit vagus nerve (Maire et al, 1984). ATP was degraded to AMP with intermediate formation of ADP, corresponding to the functional properties of NTPDase2, but not NTPDase1 (Zimmermann, 2001).…”

Receptor-mediated calcium signalling in glial cells from mouse corpus callosum slices

“…There are intimate contacts between axons and a variety of glia, including the myelinating oligodendrocytes, 0 2 A glial progenitor cells, and astrocytes that send processes to the axonal surface (Raff, 1989). Even though there are no known vesicular mechanisms for releasing neuroactive substances in white matter, nerve fiber tracts in certain vertebrates have been shown to release glutamate (Weinreich and Hammerschlag, 1975) and adenosine (Maire et al, 1984) during electrical stimulation.…”

“…Also, the nonvesicular release of adenosine, ATP, and glutamate from axons after electrical stimulation has been found in the squid axon (Chiu and Kriegler, 1994 and refs. therein) and mammalian PNS and CNS preparations (Weinreich and Hammerschlag, 1975;Maire et al, 1984;Manzoni et al, 1994).…”

Role of Endogenous Adenosine as a Modulator of Syncope Induced During Tilt Testing

“…8 Nevertheless, ATP and adenosine are also released by sympathetic fibers 26,27 and by poorly myelinated or nonmyelinated fibers, including C fibers. 28 The activation of myocardial mechanoreceptors, which are C fibers, is thought to be one of the mechanisms underlying vasodilatation and hypotensioninduced syncope. 1,28,29 Thus, we hypothesize that the activation of these fibers and increased sympathetic tone may be involved in adenosine release into the extracellular space.…”

“…28 The activation of myocardial mechanoreceptors, which are C fibers, is thought to be one of the mechanisms underlying vasodilatation and hypotensioninduced syncope. 1,28,29 Thus, we hypothesize that the activation of these fibers and increased sympathetic tone may be involved in adenosine release into the extracellular space. Even if there is no objective evidence for an increased sympathetic activation in patients with higher adenosine baseline levels (eg, similar heart rate and blood pressure), it can be hypothesized that sympathetic activation could be counterbalanced and masked by the effects of high adenosine concentration, which decreased heart rate and blood pressure.…”