Abstract
The effects of alpha receptor block and inhibition of neuronal uptake on the release and metabolism of 3H-norepinephrine (3H-NE) were evaluated in the isolated, perfused cat spleen. Phenoxybenzamine and phentolamine are more potent as blockers of the alpha receptor than as inhibitors of the uptake of L-3H-NE. Cocaine and phenoxybenzamine are equipotent in inhibiting removal of 3H-NE ; phentolamine is approximately 100 times less potent. At least a 30-fold greater concentration of both phenoxybenzamine and cocaine is required to induce release of 3H-NE than is required to inhibit uptake of the catecholamines. The concentration of phentolamine which increases the spontaneous efflux of total 3H is identical to that required to inhibit neuronal uptake of NE. 3H-3,4-dihydroxyphenylethyleneglycol represents nearly 60% of the total spontaneous efflux of radioactivity from spleens previously labeled with L-3H-NE. 3H-3,4-dihydroxymandelic acid constitutes less than 4% of the total radioactivity. Selective inhibition of neuronal uptake of NE affects the metabolite pattern of spontaneously released 3H-NE only by producing a slight increase in the percentage of unchanged NE in the effluent. It therefore appears that most of the 3H-3,4-dihydroxyphenylethyleneglycol which is released spontaneously is formed from 3H-NE which leaks from the granules into the cytoplasm of the nerve ending and which is deaminated by intraneuronal monoamine oxidase. The O-methylated NE metabolites presumably arise from extraneuronal O-methylation of 3H-NE and the 3H-deaminated metabolites of NE, since there is a selective decrease in the proportion of these metabolites when concentrations of phenoxybenzamine or phentolamine known to inhibit extraneuronal uptake are perfused through the spleen.
Footnotes
- Received May 7, 1973.
- Accepted September 27, 1973.
- © 1974 by The Williams & Wilkins Co.
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