Adenosine is released per se under physiological conditions from the rat striatum in vivo


Adenosine is released per se under physiological conditions from the rat striatum in vivo

Pedata, F.; Melani, A.; Corti, F.; Stephan, H.; Müller, C. E.; Vannucchi, M. G.

In this study, extracellular concentrations of adenosine and ATP from the rat striatum were estimated by the microdialysis technique under physiological conditions and during focal cerebral ischemia induced by middle cerebral artery occlusion (MCAo). Under these conditions, adenosine and ATP concentrations were in the range of 130 nM and 30 nM, respectively. Blocking the ecto-ATPases with the novel inhibitor polyanion [TiW11CoO40]8- (PV4: 100 μM), recently synthesized and characterized by Stephan and Müller, we could demonstrate that the extracellular concentration of ATP increased 12-fold and that adenosine concentration was not modified. This result indicates that, under physiological conditions, adenosine is released per se from cells. In the presence of PV4 and of the adenosine equilibrative transporter inhibitor dipyridamole (100 μM), adenosine extracellular concentration was increased 3-fold. This result excludes the possibility that adenosine is carried out of cells by a carrier mediated efflux. By using immunolabeling and electron microscopy, we showed the presence of the CNT2 on plasma membrane of synaptic terminals and on vesicle membranes. Results suggest that under in vivo physiological conditions adenosine is transported in vesicles and is released in an excitation-secretion manner.
In the first 4 hours after in vivo ischemia induced by MCAo, adenosine increased to ~690 nM and ATP to ~50 nM. In the presence of PV4 the extracellular concentration of ATP increased to ~440 nM and extracellular adenosine decreased to ~270 nM. An upregualtion of ecto-nucleotidases after ischemia might represent an important mechanism in hydrolysis of ATP and formation of extracellular adenosine in the first hours after ischemia.

  • Lecture (Conference)
    International Conference on Purinergic Drugs and Targets 2011, 22.-25.07.2011, Bonn, D
  • Open Access Logo Abstract in refereed journal
    Purinergic Signalling 8(2012)1, 132
    ISSN: 1573-9538

Permalink: https://www.hzdr.de/publications/Publ-15574
Publ.-Id: 15574