AJP - Renal Physiology, Vol 252, Issue 6 1103-F1111, Copyright © 1987 by American Physiological Society
Quinidine effect on hydrosmotic response of collecting tubules to vasopressin and cAMP
M. Lorenzen, G. Frindt, A. Taylor and E. E. Windhager
Quinidine, a compound thought to increase cytosolic calcium ion activity,
has been found to inhibit the hydrosmotic response to vasopressin (VP) and
adenosine 3',5'-cyclic monophosphate (cAMP) in the toad urinary bladder. To
test whether this drug has a similar action in the mammalian nephron, the
effect of quinidine on the hydraulic conductivity of the isolated perfused
rabbit cortical collecting tubule (CCT) exposed to either 20 microU/ml VP
or 10(-4) M 8-(p-chlorophenylthio) - adenosine 3',5' - cyclic monophosphate
(8-CPT-cAMP) was studied. Quinidine had no effect on the basal water
permeability of the CCT. Quinidine sulfate (10(-4) M) reduced the
VP-stimulated water permeability from 280 +/- 50 X 10(-7) to 115 +/- 41 X
10(-7) cm X s-1 X atm-1 (P less than 0.05). The hydrosmotic response to
8-CPTcAMP was likewise reduced following exposure to quinidine. This effect
was shown to be dose dependent. In paired experiments, inhibition of the
response to 10(-4) M 8-CPTcAMP averaged 11% at 10(-6) M, 27% at 5 X 10(-6)
M, 53% at 5 X 10(-5) M, and 50% at 10(-4) M quinidine. Inhibition of the
response to 8-CPTcAMP was estimated to be half maximal at approximately 5 X
10(-6) M quinidine. Tubules were protected against the quinidine-induced
inhibition by the addition of 6.5 X 10(-5) M quin 2-acetoxymethylester in
the presence of low peritubular Ca concentration. These results are
consistent with the view that elevated cytosolic Ca ion levels inhibit the
increase in water permeability elicited by VP or exogenous cAMP in the
mammalian CCT.
