purinergic

Purinergic signaling refers to extracellular communication mediated by purine nucleotides and nucleosides, especially ATP, ADP, AMP, and adenosine. These molecules can be released by cells in response to stress, injury, or normal physiological activity and act on specific receptors to influence a wide range of biological processes.

Two main classes of purinergic receptors are involved. P1 receptors, also known as adenosine receptors, are G protein-coupled and include A1, A2A, A2B, and A3 subtypes. P2 receptors are divided into P2X ion channel receptors (P2X1 through P2X7) and P2Y G protein-coupled receptors (several subtypes such as P2Y1, P2Y2, P2Y4, P2Y6, and others). ATP and ADP act as endogenous ligands for these receptors, with adenosine primarily engaging the P1 receptor family.

Metabolism of extracellular nucleotides shapes purinergic signaling. Ectonucleotidases, including CD39 (ENTPD1) and CD73 (5′-nucleotidase), sequentially hydrolyze ATP to ADP, AMP, and adenosine, thus regulating signal duration and intensity. The balance between ATP/ADP signaling and adenosine signaling can produce opposing physiological effects.

Purinergic signaling participates in numerous physiological systems. In the nervous system, it modulates neurotransmission, glial communication, and pain processing. In the immune system, it influences inflammation and leukocyte activity. In the cardiovascular system, it affects vasodilation and platelet aggregation, with P2Y12 as a notable target for antithrombotic drugs. Purinergic pathways also impact cancer progression and tissue repair, making them relevant to various disease contexts.

The concept and receptors were first proposed by Geoffrey Burnstock in 1972, and the field has since evolved into a broad area of study with ongoing therapeutic interest, including selective receptor antagonists and enzyme modulators.