Nitric Oxide and Cyclic GMP

NITRIC OXIDE AND CYCLIC GMP

Eukaryotic cells use several other second messengers. These include cyclic GMP (cGMP) , Ca 2+ ions, inositol triphosphate, and other products derived from the membrane lipid phosphatidylinositol. Cyclic GMP is made from GTP by the enzyme guanylate cyclase . There are two different types of guanylate cyclases. One is membrane bound and also functions as a receptor for peptide hormones. The other is a soluble protein found in the cytoplasm that is activated by nitric oxide ( Fig. 19.12 ). Cyclic GMP controls ion channel opening and closing, and it activates gene expression via protein kinases. Cyclic GMP-dependent protein kinase is capable of entering the nucleus where it regulates gene transcription by phosphorylating certain transcription factors, such as Oct-1.

Nitric oxide is unusual in being a gaseous signal molecule. Whether it should be regarded as a hormone or a neurotransmitter is debatable, because its action has characteristics of both types of signals. Nitric oxide acts via cyclic GMP. Nitric oxide (NO) is short-lived and is involved in control of a variety of local cellular activities, including the contraction of blood vessel walls. In response to nerve cell signals, NO is made from arginine and oxygen by Nom synthase in endothelial cells and diffuses into nearby muscle cells. Here it binds to a heme cofactor attached to guanylate cyclase and triggers cGMP production ( Fig. 19.13 ). This leads to muscle relaxation and dilation of blood vessels. (Nitric oxide at higher levels is toxic and is made as an antibacterial agent by activated immune cells.)