The natriuretic peptide receptor-A (NPR-A) is composed of an extracellu-lar ligand-binding domain, a transmembrane-spanning domain, a kinase homology domain (KHD) and a guanylyl cyclase domain. Because the presence of ATP or adenylylimidodiphosphate reduces atrial natriuretic peptide (ANP) binding and is required for maximal guanylyl cyclase activ-ity, a direct interaction of ATP with the receptor KHD domain is plaus-ible.