Atrial natriuretic peptides inhibit conductive sodium uptake by rabbit inner medullary collecting duct cells.
The inner medullary collecting duct (IMCD) effects net sodium reabsorption under the control of volume regulatory hormones, including atrial natriuretic peptides (ANP). These studies examined the mechanisms of sodium transport and its regulation by ANP in fresh suspensions of IMCD cells. Sodium uptake was inhibited by amiloride but insensitive to furosemide, bu-metanide, and hydrochlorthiazide. These results are consistent with uptake mediated by a sodium channel or Na+/H+ exchange. To determine the role of sodium channels, cells were hyperpolarized by preincubation in high potassium medium followed by dilution into potassium-free medium. Membrane potential measurements using the cyanine dye, Di(S)-C3-5 verified a striking hyperpolarization of IMCD cells using this protocol. Hyperpolarization increased the apparent initial rate of sodium uptake fourfold. Amiloride and ANP inhibited potential-stimulated sodium uptake 73% and 65%, respectively; the two agents together were not additive. Addition of 5 mM sodium to hyperpolarized cells resulted in a significant amiloride-sensitive depolarization. Half-maximal inhibition of potential-driven sodium uptake occurred at 3 X 10(-7) M amiloride, and 5 X 10(-11) M ANP. We conclude that sodium enters IMCD cells via a conductive, amiloride-sensitive sodium channel, which is regulated by ANP. ANP inhibition of luminal sodium entry in the IMCD appears to contribute to the marked natriuretic effect of this hormone in vivo.
Zeidel
M L
ML
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Kikeri
D
D
Silva
P
P
Burrowes
M
M
Brenner
B M
BM
D000584:Amiloride; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007679:Kidney Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008536:Meglumine; D008564:Membrane Potentials / Q000187:drug effects; D011189:Potassium Chloride; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D011189:Potassium Chloride; D008536:Meglumine; D000584:Amiloride; D009320:Atrial Natriuretic Factor; D012964:Sodium