ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine‐mediated inhibition of release

Abstract

ATP and glutamatergic synaptic currents were compared in slices of rat medial habenula nucleus using whole‐cell patch‐clamp techniques. In most cells low voltage stimulation resulted in glutamatergic responses and not purinergic responses. In five cells where ATP currents could be stimulated with low voltages, wash out of glutamate antagonists did not reveal evoked glutamate currents. Spontaneous glutamate currents confirmed washout of antagonist. Modulation of release probability of glutamate and ATP, assessed by changes in failure rate of synaptic currents, was compared under conditions of different stimulation frequencies and in the presence of adenosine agonists and antagonists. ATP release, but not glutamate release, was shown to be modulated by increased stimulation frequency which resulted in inhibition of ATP release via A2‐like adenosine receptors. A1 receptors caused inhibition of both ATP and glutamate release. Endogenous adenosine inhibited glutamate release via A1 receptors but only inhibited ATP release via A2‐like receptors. Attempts to inhibit the degradation of ATP to adenosine did not alter the frequency dependence of the failure rate. We conclude, from the direct demonstration and from the differences in pharmacology and frequency dependence of the modulation of release, that ATP and glutamate responses are due to release from separate neurones.

Transducing system operated by adenosine A2A receptors to facilitate acetylcholine release in the rat hippocampus

“…This had already been proposed in other reports (e.g. Barraco et al, 1995Barraco et al, , 1996Li and Henry, 1998;Okada et al, 2001;Phillis, 1998;Robertson and Edwards, 1998). However, the pharmacological and biochemical data presented in these studies do not allow distinguishing between typical striatal-like adenosine A 2A receptors and atypical receptors and/or binding sites recognized by adenosine A 2A receptor agonists.…”

In vivo studies of the release of adenine 5′‐nucleotides, adenosine, and its metabolites from the rat brain

“…Here, rapid breakdown of the ATP in the synaptic cleft not only protects neurons from the excessive Ca 2+ influx initiated by receptor activation, but also results in the formation of adenosine which then curtails further ATP release [Edwards, 1996]. It has been suggested that in the medial habenula ATP and glutamate are released from separate neurons, although it may be coreleased with GABA and glycine [Robertson and Edwards, 1998;Robertson et al, 2001].…”

Molecular Physiology of P2X Receptors

“…In the case of the hippocampus, the synaptic currents are potentiated by zinc (10 M), consistent with the involvement of a P2X 2 or P2X 4 subunit. There is evidence that distinct presynaptic fibers release ATP and glutamate in the medial habenula, because release of glutamate (but not ATP) is selectively inhibited by adenosine acting at presynaptic A 1 receptors (383). The amplitudes of the ATP-mediated synaptic currents recorded are uniformly small (typically 20 -50 pA) compared with EPSCs mediated by excitatory amino acids (typically Ͼ1 nA), and this certainly raises questions regarding the physiological circumstances under which such synaptic transmission comes into play.…”