Some Inexact Methods for the Analysis of Transport Kinetics Using Dual Tracers

Abstract

Paired tracer dilution studies have provided a revolution in understanding the cellular transport of metabolites and other biologically active substances. The potency of the method lies in the twin features of selectivity and speed. Selectivity is obtained by the test tracer being paired with a reference tracer which, ideally, differs only in the features under investigation. Speed is obtained by perfusion against or close to the active site of transport. Over the last forty years the techniques have been developed by many laboratories using whole organ perfusion of the capillary bed to give rapid access to the transporting cells (see Yudilevich, this book). More recently the perfusion of cultured cells on carrier beads (see Mann, Sherrif, Toothill and Pearson, this book) have proved to allow a similar access time. It is thus rather surprising to discover that there is no consensus of how to interpret the results obtained by these methods. Old equations have been applied to new techniques with scant regard for the fundamentals of the method. New analytical methods have come, and gone, without apparently being able to fully exploit the obvious experimental power of the dilution technique. This article briefly describes the analytical problems and considers the options available to overcome them.