Guanylyl Cyclase: A Cell-Surface Receptor Throughout the Animal Kingdom

The enzyme guanylyl cyclase occurs in both soluble and membrane-associated forms, and catalyzes the formation of the second messenger cyclic GMP. The membrane forms of guanylyl cyclase encompass a family of cell-surface receptors that mediate the biological activity of a variety of peptide ligands. Representatives of this receptor family have been identified in such diverse species as rats and sea urchins. In echinoderm spermatozoa, guanylyl cyclase is a receptor for egg-associated peptides, eliciting species-specific effects, including changes in sperm respiration and motility, and a chemotactic response. In mammals, the family of guanylyl cyclases includes receptors for natriuretic peptides, as well as the target of bacterial heat-stable enterotoxins. The identification of natriuretic peptides in amphibians, birds, and fish suggests that guanylyl cyclase receptors play a role in osmotic balance in a variety of organisms. Molecular cloning evidence implies that homologs of the mammalian guanylyl cyclase receptors exist in other vertebrates, and perhaps even in invertebrates. Guanylyl cyclases thus represent an example of receptors that have diversified to serve both as external chemoreceptors and as internal hormone receptors.