Mechanism of action of indirectly acting sympathomimetic amines

The mode of action of indirectly acting sympathomimetic amines was analysed in the rat vas deferens (preloaded with 3H-(-)-noradrenaline). When monoamine oxidase (MAO), catechol-O-methyltransferase and vesicular uptake were inhibited (i.e., when the concentration of 3H-noradrenaline in the axoplasm was high), all substrates of neuronal uptake induced a carrier-mediated outward transport of 3H-noradrenaline, in strict dependence on the Km for neuronal uptake of the substrate. However, when MAO and vesicular uptake were not inhibited, some of the substrates of neuronal uptake were better releasers of 3H-noradrenaline than others; obviously, when the axoplasmic 3H-noradrenaline concentration is very low (intact vesicular uptake, intact MAO), a 'mobilization' of vesicular 3H-noradrenaline is a prerequisite for substantial release.