Na+/H+ exchange in porcine cerebral capillary endothelial cells is inhibited by a benzoylguanidine derivative.
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.
Schmid
A
A
Max-Planck-Institut für Biophysik, Frankfurt/Main, Germany.
Scholz
W
W
Lang
H J
HJ
Popp
R
R
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002196:Capillaries; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006146:Guanidines / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine
D002352:Carrier Proteins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine; C039465:5-dimethylamiloride; D000584:Amiloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D012964:Sodium