LUMINAL TRANSPORT-SYSTEM FOR H+ ORGANIC CATIONS IN THE RAT PROXIMAL TUBULE - KINETICS, DEPENDENCE ON PH - SPECIFICITY AS COMPARED WITH THE CONTRALUMINAL ORGANIC CATION-TRANSPORT SYSTEM/

The efflux of radiolabelled organic cations from the tubular lumen int o proximal tubular cells was investigated by using the stop-flow micro perfusion method. The efflux rate increased in the sequence: N-1-methy lnicotinamide (NMeN(+))< cimetidine < tetraethylammonium (TEA(+))< N-m ethyl-4-phenylpyridinium (MPP(+)). Preloading the animals by i.v. infu sion or pre perfusion of the peritubular capillaries with NMeN(+) incr eased the efflux rate of MPP(+). Luminal efflux was also augmented whe n the tubular solution was made alkaline with HCO3- or phosphate, wher eby HCO3- is more effective than phosphate. Replacement of Na+ by Csshowed no effect. With i.v. preloading the animals with NMeN(+) and wi th 25 mM HCO3- in the luminal perfusate the 2-s effflux follows kineti cs with a Michaelis constant K-m = 0.21 mmol/l and maximal flux J(max) = 0.42 pmol . cm(-1). s(-1) and a permeability term with P=37.7 mu m( 2) . s(-1). Comparing the apparent luminal inhibitory constant values for MPP(+) (Ki(l,MPP+)) with the apparent contraluminal Ki(cl,NMeN+) v alues of substrates of homologous series, it was found that (1) limita tion by molecular size occurs at the contraluminal cell side earlier t han at the luminal cell side; (2) affinity increases with hydrophobici ty of the substrates at the luminal cell side, with a steeper or equal slope than at the contraluminal cell side; (3) affinity increases wit h basicity (i.e. pKa values) at the luminal cell side with a steeper s lope than at the contraluminal cell side. Taken together, substrates w ith low hydrophobicity and low basicity interact at the luminal cell s ide more weakly than at the contraluminal cell side. On the other hand large, hydrophobic substrates have, at the luminal cell side, a highe r affinity than at the contralumi nal cell side. Many substrates, howe ver, have equal affinity at the luminal and contraluminal cell sides.