Signal transduction: activation of the guanylate cyclase-cyclic guanosine-3'-5' monophosphate system by hormones and free radicals.

Abstract

Intracellular communication and transmission of messages for many hormones and free radicals occur after the hormones and free radicals bind to their receptors by enhancing the activity of guanylate cyclase, the enzyme that catalyzes the conversion of guanosine triphosphate to the intracellular messenger cyclic guanosine-3'-5' monophosphate (cyclic GMP). The guanylate cyclase-linked receptors exist intracellularly (ie, cytoplasmic) and in membrane-bound forms. Enhancement of guanylate cyclase by hormones or free radicals increases intracellular cyclic GMP, which closes cation channels in the kidney while activating cation channels in the retina and olfactory cilia, either directly or by cyclic GMP-dependent protein kinase. Cyclic GMP also has potent blood pressure lowering properties. Cyclic GMP promotes growth by increasing DNA, RNA, and protein synthesis. Overactivity of this system is observed in Traveler's diarrhea, whereas underactivity occurs in Chediak-Higashi syndrome in which lysosomal enzyme release and chemotaxis are defective and can be corrected in vitro by addition of cyclic GMP.