Effects of trifluoperazine and verapamil on the hydro-osmotic response to antidiuretic hormone in the urinary bladder of the toad.

Abstract

To investigate the role of the intracellular calcium-calmodulin complex in the hydro-osmotic response to antidiuretic hormone (ADH), the effects of trifluoperazine (TFP), a well-established inhibitor of calmodulin-mediated functions, and of verapamil (V), a calcium entry blocker, were examined in the urinary bladder of the toad, a model for the late distal tubule and the collecting duct of the mammalian nephron. Preincubation of the hemibladders with TFP at serosal concentrations of 10(-5) and 10(-4) M was without effect on basal water flow but markedly reduced the maximal hydroosmotic response to ADH (50 mU/ml) in a dose-dependent manner as compared to control hemibladders (23.60 +/- 1.23 vs. 42.17 +/- 4.18 mg/min per hemibladder (10(-5) M TFP) and 5.43 +/- 0.59 vs. 52.50 +/- 4.67 mg/min per hemibladder (10(-4) M TFP). This inhibitory effect of TFP on the ADH-stimulated osmotic water flow persisted in the presence of naproxen (10(-5) M), a known inhibitor of prostaglandin synthesis. The hydro-osmotic response to cyclic adenosine 3',5' monophosphate (cAMP, 10(-3) M) was also significantly reduced in TFP-pretreated tissues (11.68 +/- 1.84 vs. 32.83 +/- 3.14 mg/min per hemibladder), suggesting a post-cAMP inhibitory effect of TFP. V (10(-4) M) had no effect on basal water flow but significantly reduced the hydro-osmotic effect of 50 mU/ml ADH (15.17 +/- 1.05 vs. 38.00 +/- 3.39 mg/min per hemibladder). In contrast, cAMP-stimulated osmotic water flow was significantly stimulated in V-treated tissues (48.07 +/- 1.95 vs. 27.13 +/- 1.50 mg/min per hemibladder).(ABSTRACT TRUNCATED AT 250 WORDS)