Release of3H-dopamine and Analogous monoamines from rat striatal tissue
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The release of previously accumulated3H-dopamine (DA) from minces of striatal tissue prepared from the brains of pargyline-pretreated rats was evaluated by superfusion with a physiological buffer solution in a six-chamber apparatus with silver toroid electrodes to provide electrical field stimuli. The identity of released tritium as3H-DA was demonstrated chromatographically and3H-DA taken up was found in a synaptosomal subcellular fraction.
Release of3H-DA previously accumulated at 0.3µM was found to be linearly dependent on stimulus intensity between 1 and 10 V (for 60 sec); 5 V was selected as a standard stimulus.
Release of3H-DA did not occur from minces of rat liver, nor was there release of previously accumulated labeled urea or leucine from striatal tissue by electrical stimulation, 50 mM KCL, or 0.1 mM (+)-amphetamine. When3H-DA was taken up in the presence of cocaine (1 mM) or benztropine (100µM), electrically induced release of3H-DA was markedly reduced, while spontaneous efflux was much less altered.
Release of3H-DA was also induced by depolarizing concentrations of K+, as well as by Rb+ or NH 4 + , and by veratridine. Electrical release and that induced by 50 mM K+ or 100µM veratridine was blocked by the omission of Ca2+ (with EDTA added) and that induced by veratridine was blocked by tetrodotoxin (30µM).
While Mg2+ and Mn2+ had little effect on electrical release of3H-DA, Li+ had a clearly inhibitory effect (IC50, ca. 0.3 mM).
Other monoamines induced significant efflux of3H-DA from unstimulated tissue, in descending rank order of effectiveness:p-tyramine > (+)-α-methyl-tyramine (p-hydroxyamphetamine) ⩾ (+)-amphetamine > (−)-amphetamine = 5-hydroxytryptamine (serotonin) = (±)-p-hydroxynorephedrine.
Other tritiated monoamines, previously accumulated at 0.3–0.7µM, were also released by electrical stimulation in the following descending rank order: (±)-octopamine ⩾ tyramine ⩾ (±)-norepinephrine = dopamine = (±)-metaraminol = (±)-α-methyltryamine » (±)-normetanephrine = 3-methoxytyramine.
Electrical release of3H-DA was largely unaffected by reserpine pretreatment [in the presence of a monamine oxidase (MAO) inhibitor]; release of tritiated tyramine, metaraminol, norepinephrine, and especially octopamine, was somewhat more reserpine sensitive.
These results indicate that3H-DA, previously accumulated by highaffinity uptake, can be released by electrical, ionic, or other depolarizing stimuli, and its efflux increased by monoamines [such as (+)-amphetamine] that also compete for uptake. Depolarization-induced release was highly calcium dependent, was inhibited by tetrodotoxin, and was strongly inhibited by lithium. Severalp-hydroxy analogues of DA or amphetamine (but not their 3-methoxy congeners) also were released by electrical-field stimulation, suggesting that they may be able to act as alternative or “false” transmitters in DA nerve terminals of the mammalian brain.
Key wordsamphetamines dopamine false transmitters lithium release striatum
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