Abstract
Isolated rat and guinea-pig atria were labeled with tritiated norepinephrine. The proportions of tritiated norepinephrine and its metabolites released during spontaneous activity and electrical stimulation were estimated. The spontaneous outflow of tritiated compounds from guinea-pig atria contained 90% metabolic products of norepinephrine, chiefly those formed by monoamine oxidase alone. Field stimulation caused a 2- to 3-fold increase in radioactive outflow, of which 40% was present as deaminated metabolites and 60% as norepinephrine. Stimulation did not increase formation of deaminated O-methylated metabolites. Normetanephrine, the O-methylated amine, was not formed by guinea-pig atria either spontaneously or after field stimulation. Inhibition of monoamine oxidase by pargyline pretreatment caused small amounts of normetanephrine to be formed by spontaneously beating atria, but all of the stimulus-induced release was present as unchanged norepinephrine. Rat atria (normal and monoamine oxidase inhibited) metabolized tritiated norepinephrine in nearly the same way as did guinea-pig atria. A shift from deamination to O-methylation did not occur after inhibition of monoamine oxidase. In contrast, rat vas deferens formed an increased amount of normetanephrine during field stimulation when monoamine oxidase was inhibited. Blockade of reuptake of norepinephrine into nerve terminals by phenoxybensamine, cocaine or desipramine did not prevent the formation of deaminated metabolites by the spontaneously beating atria. However, when the atria were stimulated electrically, nearly all of the increased radioactivity was unchanged norepinephrine, indicating that a fraction of the norepinephrine released by stimulation is normally taken up again into the nerve terminal where some of it is metabolized by monoamine oxidase and escapes as a deaminated product.
Footnotes
- Received March 22, 1971.
- Accepted July 12, 1971.
- © 1971 by The Williams & Wilkins Co.
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