Effect of trifluoperazine on rabbit cortical collecting tubular response to vasopressin.
Anuran membrane studies suggest that the calcium-binding protein calmodulin is necessary for arginine vasopressin (AVP) to exert a hydro-osmotic effect. We therefore examined the effect of trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphtholene sulphonamide (W-7), chemically dissimilar calmodulin inhibitors, on hydraulic conductivity (Lp) response to AVP in rabbit cortical collecting tubules perfused in vitro. Trifluoperazine but not W-7 increased basal Lp in rabbit cortical collecting tubules. When cortical collecting tubules were pre-treated with either trifluoperazine or W-7, the effect of AVP to increase Lp was significantly inhibited. To determine the site of this inhibition, Lp responses to exogenous cyclic adenosine 3',5'-phosphate (AMP) were studied. Both trifluoperazine and W-7 pretreatment significantly inhibited the effect of a cyclic AMP analogue to increase rabbit cortical collecting tubule Lp. These results suggest that calmodulin may be an important mediator of the hydro-osmotic response to AVP in the mammalian cortical collecting tube by acting at a site or sites distal to cyclic AMP formation.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects*; D009994:Osmolar Concentration; D009995:Osmosis / Q000187:drug effects; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology*
D002147:Calmodulin; D013449:Sulfonamides; D013873:Thionucleotides; D001127:Arginine Vasopressin; D014268:Trifluoperazine; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; C017967:W 7; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases