Category: receptor_pharmacology
Adenosine is a ubiquitous purine signaling molecule generated from ATP/AMP breakdown (extracellular via CD39 → CD73; intracellular via SAH → SAM cycle). Acts on four G-protein-coupled receptors with distinct G-coupling and tissue distribution. A1 (Gi/o-coupled, high abundance in brain, heart, kidney): ↓cAMP → ↓neurotransmitter release (sleep-promoting; "ado pressure" Borbély S process), bradycardia (cardiac AV node — therapeutic adenosine bolus for SVT), antinociception, ↓renal renin. A2A (Gs-coupled, striatum, blood vessels, lymphocytes, platelets): ↑cAMP → vasodilation (coronary — basis of dipyridamole/regadenoson stress testing), inhibits T-cell activation (immunosuppression — tumor microenvironment), antiplatelet (ticagrelor partial mechanism); striatal A2A on D2 MSNs antagonizes D2 → Parkinson target (istradefylline). A2B (Gs, lower-affinity, widely expressed): mast-cell activation, asthma + inflammation. A3 (Gi, cardioprotective, anti-tumor, anti-inflammation; pre-clinical agonists). Adenosine pharmacokinetics: ultra-short half-life (~10 s in plasma) — rapidly degraded by adenosine deaminase + cellular uptake via ENT1/2 (dipyridamole blocks uptake → ↑extracellular adenosine → potentiates stress test). Methylxanthines (caffeine, theophylline, theobromine, pentoxifylline) are non-selective adenosine receptor antagonists — explains stimulant, bronchodilator, ↑HR, ↑BP effects. Therapeutics: A1 — direct adenosine IV for SVT termination (transient AV block); A2A — regadenoson (CV-stress imaging — selective A2A, doesn't hit A1 bronchoconstriction); dipyridamole (uptake inhibitor → A2A-mediated coronary vasodilation, stress imaging + antiplatelet in CADASIL); ticagrelor partial A2A; istradefylline for Parkinson; A2B + A3 agonists/antagonists in clinical trials (cancer immunotherapy, fibrosis). Cross-links: [[caffeine_demethylation]] (xanthines), [[circadian_clock_bmal1_per_cry]] (sleep), [[platelet_aggregation]] (antiplatelet).