Saxenhofer H, Fitzgibbon W R, Paul R V
Division of Nephrology, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina.
Am J Physiol. 1993 Feb;264(2 Pt 2):F267-73. doi: 10.1152/ajprenal.1993.264.2.F267.
Urodilatin (URO) [ANP-(95-126)] is an analogue of atrial natriuretic peptide (alpha-ANP) [ANP-(99-126)] that was first isolated from human urine. In rat mesangial cells, URO competed with high affinity for non-guanylate cyclase-coupled ANPR-C receptors [concentration at which 50% labeled ligand is displaced (IC50) approximately 70 pM], but with lesser affinity to the guanylate cyclase-linked ANPR-A receptors (IC50 approximately 800 pM). alpha-ANP bound to both receptors with similar affinity [dissociation constant (Kd) approximately 150 pM]. In papillary collecting duct homogenates, which possess only ANPR-A receptors, the apparent Kd value averaged 229 pM for alpha-ANP and 2.7 nM for URO. Intravenous URO was at least as potent and effective as alpha-ANP in inducing diuresis and natriuresis in anesthetized rats, but URO was approximately 10-fold less potent in stimulating guanosine 3',5'-cyclic monophosphate generation in mesangial and inner medullary collecting duct cells. We conclude that URO has a lesser affinity than alpha-ANP for guanylate cyclase-coupled ANP receptors in the kidney and that the relative natriuretic potency of URO in vivo cannot be directly attributed to its binding characteristics with ANPR-A receptors.
尿舒张素（URO）[心房钠尿肽（ANP）-(95 - 126)]是心房钠尿肽（α-ANP）[ANP-(99 - 126)]的类似物，最初从人尿中分离得到。在大鼠系膜细胞中，URO与非鸟苷酸环化酶偶联的ANPR - C受体具有高亲和力竞争[使50%标记配体被置换的浓度（IC50）约为70 pM]，但与鸟苷酸环化酶连接的ANPR - A受体的亲和力较低（IC50约为800 pM）。α-ANP与两种受体结合的亲和力相似[解离常数（Kd）约为150 pM]。在仅具有ANPR - A受体的乳头集合管匀浆中，α-ANP的表观Kd值平均为229 pM，URO为2.7 nM。静脉注射URO在麻醉大鼠中诱导利尿和利钠作用方面至少与α-ANP一样有效，但URO在刺激系膜细胞和髓质内集合管细胞中鸟苷3',5'-环磷酸生成方面的效力约低10倍。我们得出结论，URO在肾脏中与鸟苷酸环化酶偶联的ANP受体的亲和力低于α-ANP，并且URO在体内的相对利钠效力不能直接归因于其与ANPR - A受体的结合特性。
