Effect of harmaline on organic ion transport in rabbit renal cortical slices.
The effect of harmaline on the transport of organic ions was determined in rabbit kidney cortical slices. Harmaline inhibited p-aminohippurate (PAH) uptake noncompetitively in a dose-dependent manner over the concentration range of 0.1 and 10 mM, with the 50% inhibition at 0.65 mM. Harmaline also inhibited the microsomal Na-K-ATPase activity and the tissue oxygen consumption and altered cellular Na and K contents, the effective dose being similar to that on PAH uptake. Under anaerobic conditions, harmaline inhibited Na-dependent PAH uptake in Na, K-depleted slices. Harmaline was a strong competitive inhibitor of TEA transport, showing the 50% inhibition at 8 microM. Amiloride (0.5 mM) and choline (1 mM) inhibited TEA uptake by 74 and 75%, respectively. Harmaline did not inhibit additively the TEA uptake in the presence of amiloride or choline. These results suggest that harmaline affects PAH uptake across the basolateral membrane by inhibiting Na-K-ATPase in aerobic slices, and probably by interacting with the Na sensitive site on the PAH carrier in anaerobic slices. Harmaline inhibits TEA uptake by direct action on the organic cation transport system in the basolateral membrane of the rabbit renal proximal tubule.
Kim
Y K
YK
Department of Physiology, College of Medicine, Pusan National University, Korea.
Park
Y S
YS
Lee
S H
SH
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism*; D005260:Female; D006246:Harmaline / Q000494:pharmacology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000097:blood
D000470:Alkaloids; D004573:Electrolytes; D013757:Tetraethylammonium Compounds; D006246:Harmaline; D000254:Sodium-Potassium-Exchanging ATPase; D010130:p-Aminohippuric Acid