title: Contraluminal transport of organic cations in the proximal tubule of the rat kidney. I. Kinetics of N1-methylnicotinamide and tetraethylammonium, influence of K+, HCO3-, pH; inhibition by aliphatic primary, secondary and tertiary amines and mono- and bisquaternary compounds.
abstract: In order to study the characteristics of contraluminal organic cation transport from the blood site into proximal tubular cells the stopped-flow capillary perfusion method was applied. The disappearance of N1-[3H]methylnicotinamide (NMeN+) and [3H]tetraethylammonium (TEA+) at different concentrations and contact times was measured and the following parameters evaluated: Km,NMeN = 0.54 mmol/l, Jmax,NMeN = 0.4 pmol s-1 cm-1; Km,TEA = 0.16 mmol/l, Jmax,TEA = 0.8 pmol s-1 cm-1. TEA+ inhibited NMeN+ transport and NMeN+ the uptake of TEA+. Thereby, the Ki values for inhibition correspond closely to the Km values for uptake. Similar inhibitory potencies of ten organic cation against TEA+ and NMeN+ transport provide further evidence for a common transport system. Omission of HCO3-, or Na+ and addition of K+ (with or without Ba2+) reduce NMeN+ transport, while omission of K+ (with or without valinomycin) or addition of thiocyanate has no effect. Since the manoeuvres that depolarize contraluminal electrical potential difference reduce NMeN+ transport, cell-negative electrical potential difference is suggested as a driving force for contraluminal organic cation transport from the interstitium into the cell. Furthermore, the inhibitory potency (app. Ki values) of homologous series of primary, secondary, tertiary and hydroxy amines as well as of mono- and bisquaternary ammonium compounds against NMeN+ transport was tested. The inhibitory potency increased in the sequence methyl less than ethyl less than propyl less than butyl and primary less than secondary less than tertiary amines less than quaternary ammonium compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Max-Planck-Institut für Biophysik, Frankfurt/Main, Federal Republic of Germany.
authors.forename: K J
authors.initials: KJ
authors.lastname: Ullrich
authors.forename: F
authors.initials: F
authors.lastname: Papavassiliou
authors.forename: C
authors.initials: C
authors.lastname: David
authors.forename: G
authors.initials: G
authors.lastname: Rumrich
authors.forename: G
authors.initials: G
authors.lastname: Fritzsch
mesh_terms: D000588:Amines / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002412:Cations / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011188:Potassium / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000493:pharmacokinetics
chemical_list: D000588:Amines; D001639:Bicarbonates; D002412:Cations; D000644:Quaternary Ammonium Compounds; D013757:Tetraethylammonium Compounds; D009536:Niacinamide; D019789:Tetraethylammonium; D011188:Potassium; C008472:N-methylnicotinamide