Extracellular cGMP inhibits transepithelial sodium transport by LLC-PK1 renal tubular cells

Am J Physiol. 1996 Feb;270(2 Pt 2):F283-8. doi: 10.1152/ajprenal.1996.270.2.F283.

Abstract

Both atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) inhibit tubular sodium reabsorption by generation of guanosine 3',5'-cyclic monophosphate (cGMP). To determine the role of extracellular cGMP in this response, monolayers of porcine renal tubular LLC-PK1 cells were incubated for 5 min with ANP, SNP, cGMP, or 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) (10 nM to 0.1 mM). Transepithelial sodium transport was measured as amiloride-inhibitable short-circuit current (Isc). Incubation of cell monolayers with 1 microM of ANP, cGMP, or 8-BrcGMP inhibited Isc by > 70%, as did SNP at 100 microM (P < 0.01). Adenosine 3',5'-cyclic monophosphate (0.1 mM) had no significant effect. Incubation of monolayers with 1 microM LY-83583 (an inhibitor of guanylyl cyclase), 10 microM probenecid (an organic anion transport inhibitor), or preincubation with 1 microgram/ml nocodazole (a microtubule disrupter) reduced extracellular accumulation of cGMP (P < 0.05) and abolished the SNP-mediated reduction of Isc. However, addition of these inhibitors did not affect reduction of Isc by exogenous cGMP. We conclude that SNP inhibits sodium transport by LLC-PK1 monolayers through generation of cGMP but that extrusion of cGMP out the cell is necessary for its effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / pharmacology
  • Biological Transport / physiology
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / pharmacology
  • Cyclic GMP / physiology*
  • Electric Conductivity
  • Epithelial Cells
  • Epithelium / metabolism
  • Extracellular Space / metabolism*
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism*
  • LLC-PK1 Cells / metabolism
  • Nitroprusside / pharmacology
  • Sodium / metabolism*
  • Sodium / physiology
  • Swine

Substances

  • Nitroprusside
  • 8-bromocyclic GMP
  • Atrial Natriuretic Factor
  • Sodium
  • Cyclic GMP