Wise Young
09-27-2001, 04:57 PM
Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors [Review]
R.A. Cunha
Neurochemistry International, 2000, 38:2:107-125
Manuscript received 26 October 1999 Accepted 3 February 2000;
Abstract
Adenosine exerts two parallel modulatory roles in the CNS, acting as a homeostatic modulator and also as a neuromodulator at the synaptic level. We will present evidence to suggest that these two different modulatory roles are fulfilled by extracellular adenosine originated from different metabolic sources, and involve receptors with different sub-cellular localisation. It is widely accepted that adenosine is an inhibitory modulator in the CNS, a notion that stems from the preponderant role of inhibitory adenosine A1 receptors in defining the homeostatic modulatory role of adenosine. However, we will review recent data that suggests that the synaptically localised neuromodulatory role of adenosine depend on a balanced activation of inhibitory A1 receptors and mostly facilitatory A2A receptors. This balanced activation of A1 and A2A adenosine receptors depends not only on the transient levels of extracellular adenosine, but also on the direct interaction between A1 and A2A receptors, which control each other's action.
R.A. Cunha
Neurochemistry International, 2000, 38:2:107-125
Manuscript received 26 October 1999 Accepted 3 February 2000;
Abstract
Adenosine exerts two parallel modulatory roles in the CNS, acting as a homeostatic modulator and also as a neuromodulator at the synaptic level. We will present evidence to suggest that these two different modulatory roles are fulfilled by extracellular adenosine originated from different metabolic sources, and involve receptors with different sub-cellular localisation. It is widely accepted that adenosine is an inhibitory modulator in the CNS, a notion that stems from the preponderant role of inhibitory adenosine A1 receptors in defining the homeostatic modulatory role of adenosine. However, we will review recent data that suggests that the synaptically localised neuromodulatory role of adenosine depend on a balanced activation of inhibitory A1 receptors and mostly facilitatory A2A receptors. This balanced activation of A1 and A2A adenosine receptors depends not only on the transient levels of extracellular adenosine, but also on the direct interaction between A1 and A2A receptors, which control each other's action.