In vitro inhibition of rho-aminohippurate transport by halogenated anesthetics

RD Bastron, FM Perkins and GJ Kaloyanides

The effects of four commonly used halogenated anesthetic agents (methoxyflurane, halothane, enflurane and fluroxene) on rho- aminohippurate (PAH) uptake by rabbit renal cortical slices were examined. All agents depressed PAH uptake in a linear dose-dependent manner after 60 minutes of incubation and the effect was reversible. When the data were normalized for anesthetic potency, all agents exhibited a parallel dose-response curve. Since these agents do not share a common metabolite, it is concluded that the depression of PAH transport is mediated primarily by a direct effect of the agents acting through a common pathway. Exposure of kidney slices to perithreshold concentrations of halothane and enflurane for 180 minutes did not result in a cumulative inhibitory effect on PAH transport. A slight time-dependent effect was seen with methoxyflurane. It is suggested that with prolonged exposure metabolic conversion of methoxyflurane may occur leading to further inhibition of PAH uptake.

Volume 200, Issue 1, pp. 75-80, 01/01/1977
Copyright © 1977 by American Society for Pharmacology and Experimental Therapeutics