ISSN:
1432-1912
Keywords:
Rat heart
;
Extraneuronal efflux of catecholamines
;
Carrier-mediated outward transport
;
Uptake2
;
Facilitated exchange diffusion
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The efflux of3H-catecholamines from the extraneuronal tissue of the rat heart was analysed (after inhibition of vesicular and neuronal uptake, monoamine oxidase and catechol-O-methyl transferase). In most experiments, hearts were first loaded with a tracer concentration of a3H-catecholamine and then washed out. 1. For all four catecholamines [3H-(±)-isoprenaline,3H-(±)-adrenaline,3H-(−)-noradrenaline, and3H-dopamine] the loading period resulted in virtually the same distribution pattern: most of the radioactivity distributed into “compartment III”. However, the rate constants for efflux from compartment III increased in the order3H-(−)-noradrenaline 〈3H-dopamine〈3H-(±)-isoprenaline=3H-(±)-adrenaline. 2. O-methyl-isoprenaline (OMI, a potent inhibitor of uptake2) caused a concentration-dependent and partial inhibition of the efflux of all3H-catecholamines; its IC50 (half-maximal inhibition of OMI-sensitive efflux) was very close to that for half-maximal inhibition of inward transport by uptake2. It is concluded that there is not only (OMI-resistant) diffusional efflux of3H-catecholamines, but also (OMI-sensitive) outward transport of3H-catecholamines. The contribution by each of these processes to total efflux differed considerably from one3H-catecholamine to the next. 3. U-0521 (the COMT inhibitor used in this study) inhibited the OMI-sensitive efflux of3H-noradrenaline with an IC50 of about 100 μmol/l. However, no inhibitory effect was found for 10 μmol/l U-0521. 4. During the wash-out period (see above) various unlabelled substrates of uptake2 were added to the perfusion fluid at a concentration equalling 2×K m. Dopamine, which has a very highV max for uptake2, caused a small acceleration of the efflux of3H-isoprenaline (facilitated exchange diffusion); 5-hydroxytryptamine, which has an intermediateV max for uptake2, had no effect on the efflux of3H-isoprenaline; clonidine, which has a lowV max for uptake2, inhibited the efflux of3H-isoprenaline. 5. For a total of nine unlabelled substrates (added to the perfusion fluid at 2×K m) significant correlations were obtained between the degree of inhibition of the efflux of3H-(±)-isoprenaline, on the one hand, and the logarithm of either theV max or theK m for uptake2, on the other hand. Such results might be explained by either the dissociation of the substrate from the carrier on the inside or the return of the empty carrier to the outside being the rate-limiting step in the transport cycle. This would account for the differences betweenV max-values and for the inhibitory effect of substrates with lowV max for uptake2 on the efflux of3H-isoprenaline.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00572435
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