Protease effects on adenylate cyclase in potassium-depleted rabbit kidney.
Potassium depletion in rabbits induces a renal concentrating defect in vivo and decreased hydrosmotic response to arginine vasopressin (AVP) in isolated cortical collecting tubules (CCT) perfused in vitro. The molecular basis of the AVP resistance in potassium depletion was investigated by comparing AVP-responsive adenylate cyclase activities in CCT from potassium-depleted and control rabbits. Vasopressin-responsive enzyme activity was impaired in CCT dissected from kidneys of potassium-depleted rabbits but not when kidneys were treated with collagenase to improve microdissection conditions. Potassium depletion also depressed parathyroid hormone (PTH)-stimulated adenylate cyclase activity in proximal straight tubules (PST) dissected from untreated but not collagenase-treated kidneys. Commercially available collagenase, which also contains other proteolytic enzymes, increased AVP-sensitive adenylate cyclase activity in control CCT, and trypsin treatment of CCT dissected without collagenase abolished the decrease in AVP-sensitive activity induced by potassium depletion. Inclusion of trypsin inhibitor during collagenase treatment of kidneys lowered AVP response in CCT from potassium-depleted rabbits. These results demonstrate that potassium depletion impairs hormone-sensitive adenylate cyclase of CCT (and PST) by a protease-sensitive mechanism.
Raymond
K H
KH
Department of Medicine, University of Texas Health Science Center, San Antonio.
Holland
S D
SD
Hymer
T K
TK
McKinney
T D
TD
Katz
M S
MS
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007684:Kidney Tubules / Q000201:enzymology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000494:pharmacology*; D011191:Potassium Deficiency / Q000201:enzymology*; D011817:Rabbits; D012969:Sodium Fluoride / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D010281:Parathyroid Hormone; D001127:Arginine Vasopressin; D012969:Sodium Fluoride; D010447:Peptide Hydrolases; D014357:Trypsin; D000262:Adenylyl Cyclases