Mechanisms of guanylin action via cyclic GMP in the kidney

Guanylin, uroguanylin, and lymphoguanylin are small peptides that activate cell-surface guanylate cyclase receptors and influence cellular function vi a intracellular cGMP. Guanylins activate two receptors, GC-C and OK-GC, whi ch are expressed in intestine and/or kidney. Elevation of cCMP in the intes tine elicits an increase in electrolyte and water secretion. Activation of renal receptors by uroguanylin stimulates urine flow and excretion of sodiu m, chloride, and potassium. Intracellular cGMP pathways for guanylins inclu de activation of PKG-II and/or indirect stimulation of PKA-II. The result i s activation of CFTR and/or ClC-2 channel proteins to enhance the electroge nic secretion of chloride and bicarbonate. Similar cellular mechanisms may be involved in the renal responses to guanylin peptides. Uroguanylin serves as an intestinal natriuretic hormone in postprandial states, thus linking the digestive and renal organ systems in a novel endocrine axis. Therefore, uroguanylin participates in the complex physiological processes underlying the saliuresis that is elicited by a salty meal.