The Vasopressin-Sensitive Adenylate Cyclase in Collecting Tubules and in Thick Ascending Limb of Henle's Loop of Human and Canine Kidney*

Abstract

The major tubular effects of [8-Arg]vasopressin (AVP) in regulation of renal water excretion are initiated by stimulation of adenylate cyclase (AdC) coupled with V2 receptors. We explored whether the AVP-sensitive AdC is present in both collecting tubules and the thick ascending limb of Henle's loop of human and canine kidney. In cortical collecting tubule (CCT) and medullary collecting tubules (MCT) of human kidney, AdC was markedly stimulated by AVP [maximum change from basal level (delta), +2700%] and the the nonhormonal stimulatory agent forskolin (delta, +2000%). In human CCT, the effects of both compounds were synergistic. In contrast, AVP had no effect on AdC in either the medullary (MAL) or cortical (CAL) segment of the thick ascending limb of Henle's loop of human kidney; AVP also did not stimulate AdC in CAL or MAL in the presence of forskolin. Similar to that in the human kidney, in the canine kidney, AdC in CCT and MCT was markedly stimulated by AVP and forskolin (delta, +1000%), but AVP had no effect on AdC in CAL and MAL of the canine kidney. In intact tubules dissected from dog kidney and incubated in vitro, AVP markedly increased cAMP accumulation in MCT. AVP also elicited a small but detectable increase in cAMP accumulation in MAL. From these observations, we conclude that AVP-sensitive AdC is well developed in collecting tubules, but that AVP-sensitive AdC is absent in MAL and CAL of human kidney. Likewise, in canine nephron, the AVP-sensitive AdC of MAL and CAL is rudimentary or very labile. These findings suggest that the unresponsiveness of the AdC-cAMP system to AVP in segments of the thick ascending limb of Henle's loop may be a factor that accounts for a relatively low maximum osmotic concentration of urine which can be achieved by human or canine kidneys.

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

“…However, the effect on the TAL seems to be restricted to rodents (19) and to be part of a series of adaptations of the rodent kidney that improve its urine-concentrating ability (32). Vasopressin does not stimulate adenylate cyclase in the human TAL (which, however, is sensitive to other hormones) (33,34). Thus, it may be assumed that, in this investigation, the change in sodium excretion did not depend on an increase in sodium reabsorption in the TAL.…”

Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction.

“…Autoradiographic studies using 3H-AVP and VI a and V2 antagonist show binding sites are present in outer and inner medulla (7)(8)(9)(10). AVP has been reported to stimulate adenylate cyclase activities of MTAL of rabbit, rat, and mouse kidneys, but not ofhuman and dog kidneys (12,14,38). In vitro microperfusion studies showed that AVP stimulates NaCl transport in rabbit, rat, and mouse kidneys (39,40), possibly through the V2 receptor.…”

Identification of Amino Acid Residues That Direct Differential Ligand Selectivity of Mammalian and Nonmammalian V1a Type Receptors for Arginine Vasopressin and Vasotocin

“…The primary role of AVP involves the regulation of water and solute excretion from the kidney (1,2). The other physiological functions of AVP include control of blood pressure, platelet aggregation, liver glycogenolysis and neoglucogenesis, adrenocorticotropin release from the adenohypophysis, and aldosterone secretion from the adrenal gland (3)(4)(5)(6).…”