Biomaterial Database

Stereospecificity in contraluminal and luminal transporters of organic cations in the rat renal proximal tubule. 1996

A A Somogyi, and G Rumrich, and G Fritzsch, and K J Ullrich

Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.

The effect of chirality on the interaction of substrates with the organic cation transporters in the proximal tubule of rat kidney was investigated. The apparent Ki values of the enantiomers/diastereomers of ephedrine and norephedrine and the stereoisomers of deprenyl, tranylcypromine, disopyramide, verapamil, pindolol and quinine/quinidine were determined against the contraluminal organic cation transporter, the luminal H+/organic cation exchanger and the luminal choline+ transporter, using the stop-flow luminal or contraluminal capillary microperfusion method. The ephedrine/norephedrine enantiomers/diastereomers had apparent Ki values against the contraluminal organic cation transporter in the range of 0.8 to 2.4 mM, and only norpseudoephedrine showed significant enantioselectivity. The same substrates had apparent Ki values against the luminal H+/organic cation exchanger between 3.0 and 15.0 mM, and ephedrine, norephedrine and norpseudoephedrine showed enantioselectivity. The Ki values against the luminal choline+ transporter were even higher (7.2-19.1 mM) and demonstrated no enantioselectivity. The verapamil and deprenyl enantiomers showed selectivity against the luminal choline+ transporter, as did quinine and quinidine against the contraluminal organic cation transporter. In all other instances enantioselectivity was not observed. In no case was the difference in the Ki values of the enantiomers/isomers greater than a factor of 3. The data confirm the high degree of nonspecificity of the renal organic cation transporters. Evaluation of three-dimensional molecular models of the ephedrine enantiomers/diastereomers suggests that the spatial orientations of the amino group and, to a lesser extent, the OH group and possibly the terminal CH3 group are of importance for different interactions with the transporters.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D002412	Cations	Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.	Cation
D002794	Choline	A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.	Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D015655	1-Methyl-4-phenylpyridinium	An active neurotoxic metabolite of 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to PARAQUAT, has also been used as an herbicide.	Cyperquat,1-Methyl-4-phenylpyridine,1-Methyl-4-phenylpyridinium Chloride,1-Methyl-4-phenylpyridinium Ion,N-Methyl-4-phenylpyridine,N-Methyl-4-phenylpyridinium,1 Methyl 4 phenylpyridine,1 Methyl 4 phenylpyridinium,1 Methyl 4 phenylpyridinium Chloride,1 Methyl 4 phenylpyridinium Ion,N Methyl 4 phenylpyridine
D017136	Ion Transport	The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.	Antiport,Ion Cotransport,Ion Exchange, Intracellular,Symport,Uniport,Active Ion Transport,Facilitated Ion Transport,Passive Ion Transport,Cotransport, Ion,Exchange, Intracellular Ion,Intracellular Ion Exchange,Ion Transport, Active,Ion Transport, Facilitated,Ion Transport, Passive,Transport, Active Ion,Transport, Ion
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus