Desensitization to vasopressin action in the rat kidney medulla: studies on isolated nephron segments

Because of the prominent role of the renal medulla in the elaboration of concentrated urine and the possible differential regulation of the various nephron segments, desensitization to vasopressin (AVP) was studied on freshly isolated rat medullary thick ascending limbs (MTALs) and outer medullary collecting ducts (MCDs). Desensitization was induced through intramuscular injections of 1-deamino-8-D-arginine-vasopressin (dDAVP, 2 micrograms/day for 3 days), the last of which was performed 1 h before kidney removal. The cellular response to AVP was studied by measuring cAMP accumulation in micro-dissected nephron segments. In the MTAL, we observed a marked (around 80%) and selective desensitization to AVP, the response to either glucagon or human calcitonin remaining unaltered. In the MCD, significant desensitization was observed in the presence of 1 nM AVP in the assay medium, and was no longer significant when the AVP concentration was increased to supramaximal levels (10-1,000 nM). These experiments thus reveal a clear dissociation between MTAL and MCD with regards to dDAVP-induced desensitization and extend previous observations made on target segments in the renal cortex.