Effect of peritubular [Ca] or ionomycin on hydrosmotic response of CCTs to ADH or cAMP.
To evaluate in the mammalian kidney the effect of maneuvers thought to alter intracellular [Ca2+] on the hydraulic conductivity (Lp) response to vasopressin (VP) or 8-(p-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (ClPheS-cAMP), water flow was measured in isolated perfused rabbit cortical collecting tubules (CCTs) exposed to either varying bath [Ca] or ionomycin or quin 2-acetoxymethyl ester (AM). The development of the response to VP (20 microU/ml) was enhanced 28% by lowering Ca from 1.0 to 0.1 mM, but was not altered by increasing Ca from 1.0 to 3.75 mM. When measured in the same tubule, the maintenance phase of a previously established hormone response was inhibited by acutely raising peritubular Ca from 1.0 to 3.75 mM. Exposing the tubules to 0.1 mM Ca and 65 microM quin 2-AM, inhibited by 68% the development of the response to VP compared with that observed in tubules bathed in 1.0 mM Ca Ringer without quin 2-AM. In contrast, quin 2-AM and low peritubular Ca added during the maintenance phase enhanced the VP response by 50%. The Ca ionophore ionomycin (1.0 microM) reduced the development of the VP-elicited Lp by 65% and reversibly decreased by 42% the maintenance phase of the VP-stimulated Lp in a Ca-dependent manner. A longer exposure to the ionophore was required to inhibit the development and maintenance phases of the response to 10(-4) M ClPheS-cAMP. These results are consistent with the view that transient changes in intracellular [Ca2+] may be required for the development of the hormone response but that sustained increases in cytoplasmic Ca2+ levels inhibit the development as well as the maintenance phase of the hydrosmotic response to VP or cAMP in CCTs.
Jones
S M
SM
Department of Physiology, Cornell University Medical College, New York, New York 10021.
Frindt
G
G
Windhager
E E
EE
D000465:Algorithms; D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D004987:Ethers / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D015759:Ionomycin; D007684:Kidney Tubules / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects*; D008297:Male; D009994:Osmolar Concentration; D010539:Permeability; D011817:Rabbits; D014667:Vasopressins / Q000494:pharmacology*
D000634:Aminoquinolines; D004987:Ethers; D014667:Vasopressins; D015759:Ionomycin; C035738:Quin2-acetoxymethyl ester; D000242:Cyclic AMP; D002118:Calcium