ABSTRACT
ROS-GCs ......................................................................................... 136 Acknowledgments .................................................................................................. 138 References .............................................................................................................. 139
The cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP (cGMP) function as a second messenger in different tissues such as brain, heart, kidney, lung, eye, nose, and smooth and skeletal muscle. Cyclic nucleotides are synthesized from ATP or GTP by different isoforms of an adenylate cyclase (AC) or guanylate cyclase (GC), respectively. Nine membrane-bound and one soluble AC have been described in mammals so far, and some of these isoforms show an ubiquitous tissue distribution (1). Mammalian GCs exist also in particulate and soluble forms; they are classied in
seven membrane-bound GCs (GC-A to GC-G) and six soluble GC-subunits (α1-3 and β1-3) (2-6). Membrane-bound GCs form homodimers, whereas soluble GCs operate as heterodimers consisting of an α-and β-subunit. Membrane GCs are integrated into the membrane by one transmembrane region. By this arrangement, they are activated by extracellular signaling molecules (e.g., hormones) and transmit the primary signal to subsequent intracellular steps. Whereas three GC forms operate in this manner and function as either hormone receptors, targets for bacterial enterotoxins, or targets for intestine-derived small peptides (guanylin), other forms are named orphan receptors, because no extracellular ligands that bind and regulate these GCs have been identied so far. However, the term orphan receptor is misleading for at least two of these membrane-bound GCs, which are expressed in photoreceptor cells of the mammalian retina (7-9). They are regulated by small Ca2+-binding proteins on their cytoplasmic domains (see following text).
