ISSN:
1432-1912
Keywords:
Rate constant for efflux of amine
;
Isoprenaline
;
Simulated efflux curves
;
Extraneuronal mechanism
;
Mathematical model
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1. Rat hearts were perfused with 0.1 μM 3H-isoprenaline for 10 min in the presence of 10 μM U-0521 to inhibit catechol-O-methyl transferase (COMT) and then washed out with amine-free solution. Analysis of efflux curves revealed a preferential filling of one (compartment III) of the two extraneuronal compartments described by Bönisch et al. (1974). U-0521 inhibited the efflux of isoprenaline from compartment III. Omission of U-0521 from the wash out solution quickly restored COMT activity. It was then possible to determine the rate constant for the efflux (k s) of isoprenaline from rate of efflux and amine content of tissue. 2. A procedure is developed which permits the calculation of k s from efflux curves for amine and metabolite without any need for determining the amine content of the tissue. With this procedure, k s can be determined even when there is a “bound fraction” (i.e., a second compartment, the amine content of which does not contribute to the experimentally determined efflux). The procedure is based on the fact that, for a single compartment in which the amine is metabolized and from which there is efflux of amine and metabolite, parallel efflux curves (i.e., plots of log rate of efflux against time) are obtained, if the rate constant for the efflux of the metabolite (k p) is higher than the rate constant for the loss of amine from the compartment (k system). The activity of the metabolizing enzyme determines k system and the ratio “initial rate of efflux of metabolite/initial rate of efflux of amine” (F 0). 3. A mathematical model (simulating metabolism in, and efflux of amine and metabolite from a single compartment) was used to determine the distortion of F 0 by “k system/k P” (when k P limits the efflux of the metabolite). An estimate of k s obtained from F 0 and from k system agrees well with the estimate of k s obtained directly (see 1, above).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00495551
