Figure 1. Heterodimerization of EP₁ R and β₂ AR in airway smooth muscle cells.

(A) Under basal conditions, a β₂ agonist activates a stimulatory G protein (G_s), thus stimulating adenylyl cyclase (AC) to increase cAMP production and produce bronchodilatation. (B) PGE₂ promotes the dimerization of EP₁R with β₂AR, uncoupling β₂AR from G_s, thus reducing the bronchodilator response to a β₂AR agonist. EP₁R signals through a different G protein (G_q) coupled to phospholipase C (PLC) and the formation of inositol-1,4,5-trisphosphate (IP₃), which releases calcium ions to cause bronchoconstriction, but PGE₂ alone does not activate this pathway sufficiently to induce bronchoconstriction. PIP₂, phosphatidylinositol-4,5-biphosphate.