Kohan D E
Division of Nephrology, Veterans Affairs Medical Center, Salt Lake City, Utah.
J Cardiovasc Pharmacol. 1993;22 Suppl 8:S174-9. doi: 10.1097/00005344-199322008-00047.
Exogenous endothelin-1 (ET-1) inhibits arginine vasopressin (AVP)-induced cAMP accumulation in the inner medullary collecting duct (IMCD). Because ET-1 is produced by and binds to specific receptors on the IMCD, the possibility exists that ET-1 is an autocrine regulator of AVP action in this nephron segment. To test this hypothesis, rat IMCD cells were grown on semipermeable membranes in the presence of rabbit anti-ET-1 antiserum or nonimmune rabbit serum (NRS). AVP (10(-9) M) caused a 2.5-fold greater accumulation of cAMP in confluent IMCD monolayers preincubated in ET-1 antiserum in comparison with NRS. ET-1 (10(-8) M) inhibited the AVP-induced rise in cAMP by 65% in cells preincubated in ET-1 antiserum but had no effect in NRS-treated cells. Finally, [125I]-ET-1 (30 pM) binding was increased sixfold in IMCD preincubated in anti-ET-1 antiserum. These data indicate that ET-1 causes tonic autocrine inhibition of AVP responsiveness in the IMCD.
外源性内皮素-1（ET-1）可抑制精氨酸加压素（AVP）诱导的髓质内层集合管（IMCD）中cAMP的积累。由于ET-1由IMCD产生并与其特异性受体结合，因此ET-1有可能是该肾单位节段中AVP作用的自分泌调节因子。为验证这一假说，将大鼠IMCD细胞培养在半透膜上，并分别加入兔抗ET-1抗血清或非免疫兔血清（NRS）。与NRS相比，AVP（10⁻⁹ M）使预先在ET-1抗血清中孵育的汇合IMCD单层细胞中cAMP的积累增加了2.5倍。ET-1（10⁻⁸ M）可使预先在ET-1抗血清中孵育的细胞中AVP诱导的cAMP升高抑制65%，但对NRS处理的细胞无影响。最后，预先在抗ET-1抗血清中孵育的IMCD中，[¹²⁵I]-ET-1（30 pM）的结合增加了6倍。这些数据表明，ET-1对IMCD中AVP反应性产生持续性自分泌抑制作用。
