Neuronal transporter

Figure 8.7 Schematic diagram of the proposed structure of the noradrenaline neuronal transporter showing the 12 transmembrane, hydrophobic domains with the N- and C-termini projecting towards the cell cytoplasm. Binding domains for specific ligands are thought to be within regions indicated by the solid bars. (From Stanford 1999, reproduced with permission)...

Histamine synthesis in the brain is controlled by the availability of L-histidine and the activity of histidine decarboxylase 254 Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found 254 In the vertebrate brain, histamine metabolism occurs predominately by methylation 254... 

Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found. Newly synthesized neuronal histamine is transported into TM neuronal vesicles by the vesicular monoamine transporter VMAT2 [16]. Both in vivo and in vitro studies show that depolarization of nerve terminals activates the exocytotic release of histamine by a voltage- and calcium-dependent mechanism. Once released, histamine activates both postsynaptic and presynaptic receptors. Unlike the nerve terminals from other amine transmitters, however, histaminergic nerve terminals do not exhibit a high-affinity uptake system for histamine [5, 9, 23]. Astrocytes may contain a histamine transport system. 

Larsson, O. M., Falch, E., Schousboe, A., and Krogsgaard-Larsen, P. (1991) GABA uptake inhibitors Kinetics and molecular pharmacology, in Presynaptic Receptors, and Neuronal Transporters (Langer, S. Z., Galzin, A. M., and Costentin, J., eds.), Pergamon Press, Oxford, UK, pp. 197-200. 

The neuronal transport system is the most important mechanism for removing norepinephrine. Any norepinephrine or epinephrine in the circulation will equilibrate with the junctional extracellular fluid and thus become accessible both to the receptors and to neuronal transport. Thus, neuronal transport is also an important mechanism for limiting the effect and duration of action of norepinephrine or epinephrine, whether these are released from the adrenal medulla or are administered as drugs. Neuronal uptake is primarily a mechanism for removing norepinephrine rather than conserving it. Under most circumstances, synthesis of new norepinephrine is quite capable of keeping up with the needs of transmission, even in the complete absence of neuronal reuptake. 

It is important to make a clear distinction between neuronal and vesicular transport. Neuronal transport occurs from the junctional extracellular fluid (biophase) across the cell membrane of the neuron and into the neuronal cytosol. Vesicular transport is from the neuronal cytosol across the membrane of the vesicle and into the vesicle. Although these two systems readily transport both norepinephrine and epinephrine, certain drugs will selectively inhibit one or the other transport system. 

Destruction or removal of transmitter from site of action Tolcapone (COMT inhibitor) Phenelzine (MAO inhibitor) Tricyclic antidepressants (inhibit neuronal transport) Physostigmine (cholinesterase inhibitor)... 

HSE occurs in a certain percentage of mice or rabbits following infection. The frequency of HSE in experimental infections is dependent on the pathogenic potential of the HSV-1 and the mouse strain used for experimental infection. For HSE to occur after ocular infection, the virus must enter the TG, and then spread to the CNS, or the virus directly gains access into the brain via the optic nerve. Models have also been developed in which the virus is directly inoculated into the brain. In this model, transport from the peripheral tissue the peripheral nervous system the CNS is not important. Thus, viral genes necessary for neuronal transport and spread are not crucial for virus infection if the brain is inoculated. 

Persson E, Larsson P, Tjalve H (2002) Cellular activation and neuronal transport of intranasally instilled benzo(a)pyrene in the olfactory system of rats. Toxicol Lett 133 211-219... 

Jones SR, Joseph JD, Barak LS, Caron MG, Wightman RM (1999) Dopamine neuronal transport kinetics and effects of amphetamine. J Neurochem 73 2406-2414. 

Another factor which may contribute to the persistence of foreign amines in the transmitter stores is their afiSnity for the neuronal transport system. Amines... 

As an example of the application of QD labeling, we describe below the use of QDs to measure the diffusion of a neuronal transporter. 

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