Figure 1. Purinergic receptors important in regulating epithelial ion transport.

The P1 receptors A_2A and A_2B classically signal through G_s, resulting in an increase in cAMP and activation of PKA. A rise in intracellular Ca²⁺ noted in some cells in response to A_2B receptor activation may result from receptor coupling to G_q and activation of PLC-β or from cAMP-activation of Rap2B that raises intracellular Ca²⁺ via PLC-ɛ. This rise in intracellular Ca²⁺ by either of these mechanisms likely accounts for the activation of PLA₂ that contributes to the A_2B activated Cl⁻ current. The A₁ receptor has been shown to be active in airway epithelial cell lines and evokes a Ca²⁺ response through the βγ subunits of G_i. This triggers basolateral K⁺ efflux and may trigger Cl⁻ release. P2X receptors are ligand-gated ion channels and increase cell permeability to Na⁺ or Ca²⁺. P2Y receptors classically signal through G_q, resulting in an increase in intracellular Ca²⁺ and activation of Ca²⁺-activated Cl⁻ and K⁺ channels, although a Ca²⁺-independent Cl⁻ current resulting from P2Y activation has been identified.