Na+/H+ exchange in porcine cerebral capillary endothelial cells is inhibited by a benzoylguanidine derivative

Biochem Biophys Res Commun. 1992 Apr 15;184(1):112-7. doi: 10.1016/0006-291x(92)91165-m.

Abstract

Na+/H+ exchange activity has been examined in endothelial cells isolated from porcine brain capillaries. Intracellular pH (pHi) changes were monitored using a confocal laser scanning microscope and the pH-sensitive fluorescence indicator 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF). Acid load of the brain capillary endothelial cells was performed with a NH4Cl (20 mM) prepulse. In bicarbonate-free solutions pHi recovered within 3 to 10 min. Removal of extracellular Na+ ions demonstrated that H+ extrusion after an acid load of the cells was Na+ dependent. The Na+/H+ exchange could be completely blocked by EIPA (5-(N-ethyl-N-isopropyl)amiloride) as well as by the novel inhibitor 3-methylsulfonyl-4-piperidinobenzoyl guanidine hydrochloride (HOE 694) in concentrations of 1 to 10 microM, respectively. EIPA and HOE 694 in a concentration of 0.1 microM caused a partial block of Na+/H+ exchange.

MeSH terms

  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Animals
  • Capillaries
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Cerebrovascular Circulation*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Fluoresceins
  • Fluorescent Dyes
  • Guanidines / pharmacology*
  • Hydrogen-Ion Concentration
  • Kinetics
  • Sodium / metabolism*
  • Sodium-Hydrogen Exchangers
  • Sulfones / pharmacology*
  • Swine

Substances

  • Carrier Proteins
  • Fluoresceins
  • Fluorescent Dyes
  • Guanidines
  • Sodium-Hydrogen Exchangers
  • Sulfones
  • 3-methylsulfonyl-4-piperidinobenzoyl guanidine
  • 5-dimethylamiloride
  • Amiloride
  • 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
  • Sodium