title: Affinity of different local anesthetic drugs and catecholamines for the contraluminal transport system for organic cations in proximal tubules of rat kidneys.
abstract: To study the cellular uptake of [3H]tetraethylammonium (TEA) and its inhibition by different local anesthetic drugs and catecholamines, the capillary stopped flow microperfusion method was used. [3H]TEA concentration in the peritubular capillaries decreased in a time and concentration-dependent manner. This cellular uptake of [3H]TEA could be described by a facilitated diffusion model (Jmax = 0.57 +/- 0.08 pmol sec-1 cm-1, Km = 0.28 +/- 0.01 mmol/l). Between the pKa values of the local anesthetic drugs (range, 2.8-8.9) and their apparent Ki values, a significant correlation was found (r = -0.916, n = 12). In the case of catecholamines, hydrophobic substitution in the form of an alkyl chain in the alpha-position or at the nitrogen increased the inhibitory potency, whereas hydroxyl substitution in the beta-position decreased the affinity. Except for the catecholamines with complex substitutions at the benzene ring (--CH2OH,--NHCONH2,--OOCN[CH3)2, --Cl, --NH2) the apparent Ki values of the catecholamines were directly correlated with the hydrophobicity. It is concluded that hydrophobicity and pKa are two important physicochemical parameters which influence the affinity of a molecule for the transport system for organic cations at the contraluminal side of renal proximal tubules.
authors.affiliation: Department of Pharmacology, Aachen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Brändle
authors.forename: G
authors.initials: G
authors.lastname: Fritzsch
authors.forename: J
authors.initials: J
authors.lastname: Greven
mesh_terms: D000777:Anesthetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism / Q000494:pharmacology*; D002412:Cations; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism*
chemical_list: D000777:Anesthetics; D002395:Catecholamines; D002412:Cations; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium