Figure 6.

Proposed model for the inhibition of G protein-coupled receptor activation by nitric oxide and cyclic-GMP. Nitric oxide activates guanylate cyclase, producing cGMP and activating G kinase (GK). G kinase in turn phosphorylates the TXA₂ receptor, which prevents or disrupts coupling of the receptor to its cognate GTP-binding protein G_q and thus inhibits activation of the effector, phospholipase C (PLC), preventing [Ca²⁺]_i mobilization and cellular activation. The net effect is to shift the equilibrium in resting cells between precoupled receptor and uncoupled receptor toward the uncoupled state. It is also possible that the agonist-activated receptor is a target for G kinase. In this model, NO “sets the gain” for cellular activation by G protein-coupled receptors like the TXA₂ receptor, resulting in a net decrease in platelet or vascular smooth muscle activation by physiologic agonists.