Effect of cAMP and calmodulin inhibitors on water absorption in rat proximal tubule.
The possible role of calmodulin in solute transport was examined in the kidney of the rat. Utilizing a radioimmunoassay, calmodulin was identified and quantitated in homogenates of the cortex of the kidney. The physiologic significance of these findings was examined utilizing in vivo microperfusion techniques applied to the proximal convoluted tubule of the thyroparathyroidectomized rat. The addition of dibutyryl cyclic adenosine monophosphate (cAMP) to the luminal perfusion solution resulted in a lower rate of water absorption of 1.67 +/- 0.09 nl min-1 mm-1 as compared to 2.46 +/- 0.11 in controls. The addition of either of two compounds with affinity for calmodulin, trifluoperazine (TFP) or W-13, reversed the cAMP-induced inhibition of water absorption. In the absence of cAMP, neither agent affected water absorption. Analogs of TFP and W-13 with lower binding affinities for calmodulin had no effect on water absorption and did not reverse the cAMP effect. None of the above experimental maneuvers affected the absorption of phosphate. These results demonstrate the presence of calmodulin in the kidney of the rat and suggest that calmodulin may be involved in cAMP-associated inhibition of water and electrolyte transport in the proximal tubule of the rat.
D000042:Absorption; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
D002147:Calmodulin; D013449:Sulfonamides; D014867:Water; D014268:Trifluoperazine; D003994:Bucladesine; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D011494:Protein Kinases