Figure 12.

Augmentation of bradykinin-induced IL-8 release in hTERT-airway smooth muscle cells by Epac and PKA. Activation of ERK1/2 is mediated via different GPCRs. The β₂-agonist fenoterol acts on G_s-coupled receptors inducing cAMP elevation via activation of adenylyl cyclase (AC) while forskolin directly activates AC. cAMP activates two distinct cellular effectors: PKA and Epac, followed by activation of Ras-like GTPases, such as Rap1, and ERK1/2, and subsequently induction of specific transcription factors resulting in the production of IL-8. Bradykinin also elicits ERK1/2 phosphorylation most likely via activation of G_q-coupled receptors. The dotted line represents a potential pathway which has not been fully addressed in our study. ⊥ indicates inactivation and → indicates activation, see text for further details.