Vesicles, adrenergic uptake

In addition to impairing norepinephrine storage and thereby enhancing its catabolism, reserpine impairs the vesicular uptake of dopamine, the immediate precursor of norepinephrine. Since dopamine must be taken up into the adrenergic vesicles to undergo hydroxylation and form norepinephrine, reserpine administration impairs norepinephrine synthesis. The combined effects of the blockade of dopamine and norepinephrine vesicular uptake lead to transmitter depletion. 

As was noted on p. 68, some agonists, such as amphetamine and tyra-mine, do not act directly on the adrenoceptor. Instead, they exert their effects indirectly on the adrenergic neuron by causing the release of neurotransmitter from storage vesicles. Similarly, some agents act on the adrenergic neuron, to either interfere in neurotransmitter release or alter the uptake of the neurotransmitter into the adrenergic nerve. 

Various sympathomimetic amines can be taken up into storage vesicles, leading to the stoichiometric displacement of part of the endogenous NA content (p-tyramine and -phenylethylamine). It is not clear that such amines are taken up by the same mechanism which is responsible for catecholamine uptake. For example, metaraminol is taken up by medullary vesicles by a process which does not require ATP. and is insensitive to inhibition by reserpine. Some amines, such as DA and -methylNA. appear to be taken up both by the reserpine-sensitive and reserpine-insensitive mechanisms. It may be that the latter mechanism can account for the uptake of exogenous catecholamines into storage vesicles in reserpine-treated animals, leading to a temporary restoration of adrenergic transmission. 

Free 5-HT is quickly removed from its site of action by specific uptake mechanisms. Brain slices take up 5-HT more readily than catecholamines sympathetic nerve endings in the pineal gland can also take up free 5-HT. It is thus possible to replace by 5-HT an important fraction of the catecholamines in the specific adrenergic vesicles. 

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