Fig. 3.

Adenosine A_2A receptor transduction cascade proposed for carotid body activation. O₂-limitation of oxidative phosphorylation in mitochondria activates adenylate kinase (AK), which converts two molecules of ADP into ATP and AMP. The resulting increase in the AMP/ATP ratio promotes adenosine formation from AMP in cytosol and extracellular space. Intracellular adenosine is transported extracellularly via an equilibrative nucleoside transporter. Activation of extracellular A_2A receptors stimulates cAMP formation by adenylyl cyclase (AC), which, in turn, promotes protein kinase A (PKA) inhibition of potassium currents. The resulting fall in membrane potential (ΔV_m) activates voltage-gated Ca²⁺ channels, and the rise in intracellular Ca²⁺ leads to secretion of neurotransmitters that stimulate the carotid sinus nerve.