Guanylate cyclases belong to the adenylyl cyclase class-4/guanylyl cyclase family. There are two forms of guanylate cyclase. The soluble forms, known as GCS or sGC, act as receptors for nitric oxide. The membrane-bound receptor forms, known as GC, are peptide hormone receptors. GCS, a cGMP-synthesizing enzyme, is the major receptor for the neurotransmitter nitric oxide (NO). It plays a crucial role in smooth muscle contractility, platelet reactivity and neurotransmission. GCS is a heme containing heterodimer, consisting of one alpha subunit, designated GCS-alpha-1, and one beta subunit. The heme moeity mediates NO activation, and this heme group also binds carbon monoxide, which weakly stimulates the enzyme. Both NO and CO stimulation are enhanced by the allosteric activator 3-(5'-hydroxymethyl-2'furyl)-benzyl-indazole, YC-1. YC-1 can also stimulate GCS in a NO-independent manner. Both the alpha and beta subunits are required for cGMP generation, and at least two isoforms exist for each subunit. Heterodimers consisting of alpha-1/beta-1 and alpha-2/beta-1 have been identified, and both display similar enzymatic activity.