Fig. 9

Mechanisms for PDGF-BB-induced bronchoconstriction. The contractile effect of PDGF-BB depends on the activation TP-receptors which are mainly coupled to G_α12/13 [56, 57] activating Rho/ROCK and inhibiting thereby MLCP [58]. Further, TP-receptors (TPR) are coupled to G_αq/11, leading to the formation of IP₃ and to the release of calcium from the sarcoplasmic reticulum (SR) [56, 57]. Increased cytosolic calcium levels are leading to the activation of PKC which itself inhibits the myosin light chain phosphatase (MLCP), hence the actomyosin system remains activated and contraction of SMCs is intensified [58]. In addition, increased cytosolic calcium levels provoke the activation of Rho/ROCK [58, 67]. Last, TP-receptors (TPR) are linked to G_βγ activating MAPK-signalling. MAPK-signalling supports the activation of TP-receptors, as it strengthens the activation of the cytosolic PLA₂ [52, 53], which leads to the formation of arachidonic acid (AA), serving as a substrate for the production of TXA₂ [77]. Moreover, both PDGF-BB and PDGFR stimulate the abelson tyrosine kinase (Abl) [60, 61, 78] which acts downstream on Rho/ROCK [63, 64]. In contrast, the TKI imatinib, but not SU6668, inhibits Abl [62]. The stimulation of Abl by PDGF-BB and PDGFR is important for SMCs’ contraction, as Abl supports the polymerisation of subcortical actin filaments [59] strengthening the membrane for the transmission of the force generated by the actomyosin system. Hence, the stabilization of the cytoskeleton and the crossbridge cycling reinforce each other, leading to enhanced contraction [59]