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Affinity of different local anesthetic drugs and catecholamines for the contraluminal transport system for organic cations in proximal tubules of rat kidneys

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Fritzsch,  Günter
Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max Planck Society;

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Citation

Brändle, E., Fritzsch, G., & Greven, J. (1992). Affinity of different local anesthetic drugs and catecholamines for the contraluminal transport system for organic cations in proximal tubules of rat kidneys. Journal of Pharmacology and Experimental Therapeutics, 260(2), 734-741.


Cite as: http://hdl.handle.net/21.11116/0000-0008-5117-3
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.