Quinidine effect on hydrosmotic response of collecting tubules to vasopressin and cAMP

Abstract

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.

CHLOROQUINE INHIBITS ARGININE VASOPRESSIN PRODUCTION IN ISOLATED RAT INNER MEDULLARY SEGMENTS INDUCED cAMP COLLECTING DUCT

“…Chloroquine is a weak base that increases pHi (31) that probably increases (Ca 2+ )i (28) to inhibit the increase in water permeability elicited by AVP or exogenous CAMP (30). Lorenzen, Frindt, Taylor and Windhager reported that quinidine induced elevation in (Ca 2+ )i suppressed AVP or CAMP stimulated water absorption in microperfused collecting tubules (30). This probably explains our previous observations of the absence of antidiuresis despite chloroquine-induced increases in plasma AVP concentrations (11).…”

Renal Tubular Transport of Calcium

“…Quin-Z acetoxymethyl ester, in concentrations higher than those typically used to measure cytosolic calcium concentration, is an effective buffer for intracellular calcium ions (217). When collecting tubules were treated with quin-2 acetoxymethyl ester and low bath [Cal, the inhibitory effect of quinidine on the actions of vasopressin and cAMP was prevented (134). These results strongly suggest that quin-Z acetoxymethyl ester exerts its protective effect by preventing the quinidine-induced rise in cytosolic free Ca 2 + concentration; furthermore, the quinidine-induced inhibition of the hydrosmotic response probably depends on a rise in cytosolic calcium.…”

“…In general, the conclusion has been that maneuvers thought to increase cytosolic free Ca 2 + concentration also inhibit the hydrosmotic response to both vasopressin and cAMP. Thus quinidine, a drug known to raise cytosolic Ca 2 + activity in proximal tubule cells of Necturus (135), inhibits vasopressin-and cAMP-induced water movement in toad urinary bladder (4,201,202,206) and mammalian collecting tubule (134). The calcium ionophares A23187 and X537A also inhibit the hydrosmotic response to vasopressin or cAMP in toad bladder (154).…”

“…There is abundant evidence for such a Ca + -Na + exchange mechanisms in the basolateral membrane of renal epithelial cells (72,78,92,108,134,199,219). It is unlikely that thiazides increase net calcium reabsorption by decreasing distal transepithelial potential difference and decreasing the backflux by calcium from blood to lumen as proposed in the early literature (226).…”

“…This latter observation suggests that calcium entry into the cell across the basolateral membrane via CaH -Na + exchange is involved in the inhibition of the hydrosmotic effect of vasopressin or cAMP under these experimental conditions. Analogous experiments have been performed in isolated perfused rabbit collecting tubules (134), where low serosal sodium diminishes the usual increase in hydraulic conductance produced by vasopressin or cAMP. This inhibitory effect was attenuated when bath calcium concentration was reduced.…”