Figure 7. Signaling by PAR2 in smooth muscle.

In gastric smooth muscle PAR2 receptors are coupled to G_q, G₁₃ and Gi_1/2, and stimulation of PI hydrolysis via Ga_q and Gbg_i1/2, and RhoA/Rho kinase via Ga₁₃. Initial contraction is mediated via PLC-b/Ca²⁺/MLCK pathway whereas sustained contraction is mediated via RhoA/Rho kinase pathway. Although PAR2 receptors are coupled to inhibition of cAMP via Ga _i1/2, activation of NF-kB pathway via Ga₁₃/RhoA leads to degradation of IkB and activation of PKA that result in attenuation of Rho kinase activity in a feedback mechanism via phosphorylation of RhoA at Ser¹⁸⁸ by PKA.