Adenosine A1 receptor

Class

adenosine A1 receptor antagonist — PBF-680 (Palobiofarma)

Pathway

blocks adenosine-mediated airway hyperresponsiveness/bronchoconstriction

The adenosine A1 receptor is a G-protein-coupled receptor activated by adenosine, a naturally occurring nucleoside that accumulates in tissues during stress, hypoxia, or inflammation. Through coupling to inhibitory G-proteins, A1 receptor activation dampens cyclic AMP signaling and modulates ion channel activity in multiple tissues, including airway smooth muscle, mast cells, the heart, kidney, and central nervous system. In the lungs, adenosine acting on A1 receptors contributes to bronchoconstriction and heightened airway reactivity, a phenomenon exploited clinically in bronchial challenge testing for asthma. Blocking this receptor with a selective antagonist is intended to interrupt adenosine-driven narrowing of the airways and the exaggerated responsiveness seen in conditions such as asthma and chronic obstructive pulmonary disease. Because adenosine receptors exist as several subtypes with distinct tissue distributions and physiological roles, selectivity for the A1 subtype over A2A, A2B, and A3 receptors is pursued to concentrate pharmacological effect on the bronchoconstrictive pathway while limiting interference with adenosine's other roles, such as immune regulation or cardiac rhythm control. This mechanism is broadly relevant wherever excessive airway sensitivity to inhaled or endogenous triggers underlies disease symptoms.