SIGNALING PATHWAYS FOR GUANYLIN AND UROGUANYLIN IN THE DIGESTIVE, RENAL, CENTRAL NERVOUS, REPRODUCTIVE, AND LYMPHOID SYSTEMS

Guanylin and uroguanylin are peptides that stimulate membrane guanylat e cyclases (GC) and regulate intestinal and renal function via cGMP. C omplementary DNAs were isolated encoding opossum preproguanylin and a 279-amino acid portion of a receptor-guanylate cyclase expressed in op ossum kidney (OK) cells (GC-OK). The tissue expression of messenger RN A transcripts for these signaling molecules were then compared. Northe rn and/or reverse transciption-PCR assays revealed that guanylin, urog uanylin, and GC-OK messenger RNAs are expressed in tissues within the digestive, renal, central nervous, reproductive, and lymphoid organ sy stems. Receptor autoradiography localized the receptors for uroguanyli n and guanylin to renal proximal tubules and seminiferous tubules of t estis. Synthetic guanylin and uroguanylin peptides activated the recep tor-GCs in opossum kidney cortex and in cultured OK cells eliciting in creased intracellular cGMP. Expression of agonist and receptor-GC sign aling molecules provides a pathway for paracrine and/or autocrine regu lation of cellular functions via cGMP in the digestive, renal, central nervous, reproductive, and lymphoid/immune organ systems. Uroguanylin also links the intestine and kidney in a potential endocrine axis tha t activates tubular receptor-GCs and influences renal function.