Figure 11. The NO-GC-1-cGMP pathway, steps in the way of IOP lowering. (a) NO is generated fromL-arginine by nitric oxide synthase (NOS) available in three isoforms: (i) neuronal NOS-I (nNOS), (ii) endothelial NOS-III (eNOS) and (iii) inducible NOS-II (iNOS).(b) NO binds guanylate cyclase-1 (GC-1), a heterodimeric protein capable of converting guanosine 5′-monophosphate (5′GMP) to cyclic guanosine monophosphate (cGMP). The cGMP so produced can target cGMP-gated ion channels, and activate kinase signaling cascades. (c) Phosphodiesterase enzymes (PDEs) bind to cGMP and catalyse the decomposition of cGMP into 5’GMP. PDEs act as important regulators of signal transduction mediated by cGMP. (d) The cGMP bioavailability in the cell can be increased in two ways: (i) by the use of GC-1 stimulators and activators, which increase production of cGMP, or, (ii) by the use of PDE inhibitors that prevent the decomposition of cGMP in the cell.