Effect of trifluoperazine on rabbit cortical collecting tubular response to vasopressin.

Abstract

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. © 1986 The Physiological Society