Figure 3:  The purinergic cascade.

ATP, ADP, Ap4A,  or ADO are released into the extracellular milieu from nerves or cells where they can interact to form a purinergic cascade. Ap4A can activate P2D receptors and has the potential to be hydrolysed to ADP. Ap4A can also be broken down by diadenosine polyphosphate hydrolase to give rise to ATP and ADP.  ATP acts at a variety of P2 receptors (see text) and is sequentially degraded to ADP and AMP by ectonucleotidase activity. ADP appears to be the preferred agonist for P2t receptors and P2Y1 receptors. AMP gives rise to ADO which can interact with the various P1 receptors (A1, A2A, A2B, A3). ADO activation of P1 receptors can lead to inhibitory feedback on ATP release that can lead to increased activation of KATP channels, as well as receptor modulation.  For example, activation of the A3 receptor produces a down-regulation in A1 receptor activity in hippocampus (6).  ADO can also be formed by intracellular 5'-nucleotidase activity. Receptors indicated by circles have not yet been molecularly defined.

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published 2000