Merck UK - Calbiochem: Adenosines/Purinergic Agonists and Antagonists

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Adenosines/Purinergic Agonists and Antagonists

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Adenosine receptors, also known as P₁ receptors, are classified as A₁, A₂a, A₂b, and A₃. Adenosine is an endogenous nucleoside released from metabolically active cells. It acts as a potent biological mediator that modulates the activity of numerous cell types including platelets, neutrophils and mast cells. Adenosine receptors are linked to adenylate cyclase and other effector systems via the GTP-binding proteins. Pharmacological modulation of these receptors by methylxanthines has gained significance due to their involvement in the pathophysiology of asthma. The P₂ purinergic receptors mediate the action of ATP and exhibit a far greater sensitivity to ATP than to adenosine. They are also known as ATP receptors. They are not blocked by treatment with methylxanthines. In the CNS, the ATP receptors are divided into two major classes, ionotropic (P₂X_n) and G-protein coupled (P₂Y_n) receptors. Seven subtypes of each group, P₂X and P₂Y, are reported in the literature. The overall sequence homology between P₁ and P₂ purinoreceptors is reported to be less than 20%.

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P₁ Purinergic Receptors

Receptor Subtype	G-protein Involved	Major Action
A₁	G_I	Inhibition of adenylate cyclase
A₂a	G_s	Stimulation of adenylate cyclase
A₂b	G_s	Stimulation of adenylate cyclase
A₃	G_I G_q	Inhibition of adenylate cyclase Stimulation of PI turnover

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P₂ Purinergic Receptors

Receptor Subtype	G-protein Involved	Major Action
P₂X (several)	-	Ligand-gated ion channels.
P₂Y₁	G_q G_k	Stimulates PLC and PI turnover Opens Ca²⁺-dependent K⁺ channels.
P₂Y₂ (P₂U)	G_o	Stimulates PLC and PI turnover.
P₂T	G_I	Inhibits adenylate cyclase, stimulates platelet aggregation.
P₂I	-	Inhibits adenylate cyclase in hepatocytes.

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Adenosine/Purinergic Receptor Agonists

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