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PubMed1990

Adenosine modulates a voltage-dependent chloride conductance in cultured hippocampal neurons.

Whole cell currents were recorded in cultured rat hippocampal neurons using the patch-clamp method. When the cells were held near the resting membrane potential (-60 mV) the application of adenosine (1 microM) or the adenosine analogues 2CA (100 nM) and R-PIA (40 nM) induced a steady-state inward current. This response was unchanged when extra- and intracellular media were used, in which Na+ and K+ were substituted by impermeable ions in equimolar concentrations. In contrast the current was affected by lowering the extracellular Cl- concentration and thus Cl- was considered to be the ionic carrier. Additionally an almost complete block of the current was observed after applications of DIDS (50 microM), a putative Cl- channel blocker. The modulated current was voltage-dependent and was slowly activated by hyperpolarizing voltage steps. The adenosine action was theophylline- and pertussis toxin-sensitive indicating that the modulatory effect is mediated via an A1 receptor coupled to a G protein of the Gi or Go class.

2-Chloroadenosine↗

PubMedDate not supplied

Modulation of glial cell signaling by adenosine and pharmacological reinforcement. A neuroprotective strategy?

In view of the increasing evidence that a pathological glial activation plays a significant role in the development of neurodegenerative diseases, we investigated the underlying molecular signaling as a possible target for the pharmacological therapy. Here, we are particularly focusing on the endogenous modulation of the CA2+ and cyclic nucleotide-dependent signaling by the nucleoside adenosine and its reinforcement by the xanthine derivative propentofylline (PPF). As an experimental model, we used cultured rat microglial cells and astrocytes that are immature, show a high proliferation rate, and resemble in several aspects pathologically activated glial cells. A prolonged increase of the cellular cAMP level favored the differentiation of cultured astrocytes and associated properties required for the physiological nerve cell function. On the other hand a strengthening of the cyclic nucleotide-dependent signaling inhibited potentially neurotoxic properties of cultured microglial cells. Similar effects were obtained by treatment with propentofylline, which mimicked modulatory adenosine effects and increased the intracellular level of cAMP and cGMP. Such a pharmacological glial cell conditioning, obtained by modifying the strength and the timing of these second messengers, may provide a therapy of neurodegenerative diseases in which a pathological activation of microglial cells and astrocytes is discussed to playa pathogenic role.

Adenosine↗