UPTAKE MECHANISMS FOR NEUROTRANSMITTER AMINES

The various amine uptake mechanisms associated with adrenergic, tryptaminergic and cholinergic neurons share many common features. In each case uptake is mediated by a transport mechanism which is completely dependent upon the presence of Na+ in the external medium, and which has a very high affinity for the substrate amine, with Km values in the range 0.2-1.0 .mu.M. These high affinity uptake processes are capable of generating extremely high concentration ratios between the external medium and the intraneuronal space. Such concentrative capacities are further enhanced by the fact that amines accumulated by the high affinity uptakes do not remain free in the axoplasm but are rapidly sequestered in intraneuronal amine storage vesicles, or in the case of choline rapidly converted into acetylcholine. The functional importance of dopamine and 5-HT [5-hydroxytryptamine] uptake is still unclear. If these mechanisms are involved in terminating the actions of dopamine and 5-HT after their neural release, the pharmacological considerations discussed in detail above for norepinephrine uptake should be expected to hold for these amines also. The loss of high affinity amine uptake sites following denervation, both in the periphery and in the CNS, also has an important bearing on the phenomenon of denervation supersensitivity in different transmitter specific pathways. A loss of uptake sites following sympathetic denervation of peripheral organs is known to play an important role in the immediate development of supersensitivity in such organs, and it is likely that similar phenomena also occur in the CNS and that they apply to both dopaminergic and tryptaminergic pathways as well as to noradrenergic ones.