The role of co-transported sodium in the effect of indirectly acting sympathomimetic amines

Summary

The adrenergic nerve endings of vasa deferentia of either untreated or reserpine (R) and/or pargyline (P) pretreated rats were loaded with ³H-noradrenaline; COMT was inhibited by U-0521 (U). After 100 min of wash-out with Ca²⁺-free solution, the efflux of tritium (and of ³H-noradrenaline) from the tissue was largely of neuronal origin and remained constant with time (when expressed as fractional rate of loss; FRL). After 110 min of wash-out the effect of inhibition of the Na⁺,K⁺-ATPase (by low K⁺ or ouabain) on basal and on sympathomimetic amine-induced efflux of tritium (or ³H-noradrenaline, under the condition U) was studied in paired experiments.

Inhibition of the Na⁺,K⁺-ATPase caused a time-dependent increase in the efflux of tritium (or ³H-noradrenaline) which was inhibited by desipramine.

Inhibition of the Na⁺,K⁺-ATPase also caused a time-dependent reduction of the initial rate of neuronal uptake of ³H-noradrenaline.

The effectiveness of the sympathomimetic amines tyramine and amphetamine in inducing “release” (i.e., outward-transport) of noradrenaline depended on the experimental condition: it was most pronounced under the condition RPU, followed by the condition PU and lowest under the condition U (i.e., in tissue of untreated rats). Inhibition of the Na⁺,K⁺-ATPase caused an early and transient enhancement of the “release” of noradrenaline induced by tyramine or amphetamine. This enhancement was seen already within the first min after inhibition of the ATPase, i.e., before a pronounced inhibition of uptake (of noradrenaline) and before a pronounced increase of the basal efflux was observed. It also depended on the experimental condition: RPU > PU > U; i.e., it was the more pronounced, the higher the free axoplasmic concentration of noradrenaline.

In tissues of untreated rats, tyramine increased the rate of efflux of DOPEG, whereas amphetamine decreased it.

1) Both, tyramine and amphetamine are transported by the Na⁺-dependent neuronal transport system; 2) the co-transported Na⁺ causes a local increase in the Na⁺ concentration at the inside of the neuronal plasma membrane and thereby contributes to the outward-transport of axoplasmic noradrenaline induced by indirectly acting sympathomimetic amines; however, this contribution is only of importance when the axoplasmic concentration of noradrenaline is high (RPU, PU).