The vasopressin-sensitive adenylate cyclase in collecting tubules and in thick ascending limb of Henle's loop of human and canine kidney.
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.
Ruggles
B T
BT
Murayama
N
N
Werness
J L
JL
Gapstur
S M
SM
Bentley
M D
MD
Dousa
T P
TP
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology*; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D008138:Loop of Henle / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D013045:Species Specificity
D004224:Diterpenes; D001127:Arginine Vasopressin; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases