Dopaminergic nerve terminal

Lyness, W.H. Friedle, N.M. and Moore, K.E. Destruction of dopaminergic nerve terminals in nucleus accumbens Effect on 7-amphetamine selfadministration. Pharmacol Biochem Behav 11 553-556, 1979. 

Fig. 3 Potential subunit compositions of nAChRs expressed in dopaminergic nerve terminals. A combination of ligand binding ([ H]-epibatidine and [ I]-a-conotoxin Mil), immunoprecipita-tion, and dopamine release data have led to the conclusion that rodent brain expresses a minimum of five different nAChR subtypes. Three of these (the two forms of a4p2 and a4aSP2) do not bind a-conotoxin Mil with high affinity (a-conotoxin Mll-resistant). The three a6-containing subtypes bind a-conotoxin Mil with high affinity (conotoxin Mil-sensitive). In general, the conotoxin-sensitive nAChR subtypes are activated by lower concentrations of agonist than are required to activate the a-conotoxin Mll-resistant subtypes (Salminen et al. 2007)...

Dopaminergic neurons. Dopaminergic neurons utilize the neutotransmitter DA, which is synthesized in dopaminergic nerve terminals by two out of three of the same enzymes that also synthesize NE (Fig. 5—31). However, DA neurons lack the third enzyme, namely, dopamine beta hydroxylase, and thus cannot convert DA to NE. Therefore, it is DA that is stored and used for neurotransmitting purposes. 

Matarredona E. R., Santiago M., Venero J. L., Cano J., and Machado A. (2001). Group II metabotropic glutamate receptor activation protects striatal dopaminergic nerve terminals against MPP+-induced neurotoxicity along with brain-derived neurotrophic factor induction. J. Neurochem. 76 351-360. 

The inhibitory H3 heteroreceptors on dopaminergic nerve terminals in mouse striatal slices were not activated by endogenous histamine under the experimental conditions chosen, since their blockade did not enhance the release of dopamine (Schlicker et al. 1993). In the rat nucleus accumbens in vivo, however, indirect evidence (an histamine-evoked increase in acetylcholine release) suggests that dopamine release is permanently inhibited by endogenous histamine (Prast et al. 1999a see Section 3.6). 

The results obtained from in vitro superfusion experiments are in accord with the conclusion that the cholinergic interneurons possess a D-2 dopamine receptor. Dopamine inhibits the release of [3H]-acetylcholine from neostriatal tissue however, concentrations greater than 1 are required to achieve maximal inhibition. Because dopamine is removed from the extracellular space by the dopaminergic nerve terminals, it is difficult to... 

Stimulation of the presynaptic autoreceptors inhibits tyrosine hydroxylase activity and dopamine synthesis within the dopaminergic nerve terminals in the neostriatum (97-101 however see 102 for a negative report). The effects of dopaminergic drugs which can be ascribed to an action upon the presynaptic autoreceptor include ... 

In the light of our data showing LTP to be dopamine-dependent, it seems likely that the facilitation of LTP in Mg-free conditions may be brought about by increased HFS-induced release of dopamine. Increased dopamine release occurs in Mg++-free solution due to activation of presynaptic NMDA receptors, presumably located on dopaminergic nerve terminals (Roberts and Sharif, 1978 Krebs et al., 1991a,b Desce et al., 1992). As noted above, the dopaminergic terminals on spiny projection neurons synapse in close... 

Arluison M, Died M, Thibault J (1984) Ultrastructural morphology of dopaminergic nerve terminals and synapses in the striatum of the rat using tyrosine hydroxylase immunocytochemistry a topographical study. Brain Res Bull 73 269-285. 

Krebs MO, Desce JM, Kernel ML, Gauchy C, Godeheu G, Cheramy A, Glowinsky J (1991a) Glutamatergic control of dopamine release in the rat striatum evidence for presynaptic N-methyl-D-aspartate receptors on dopaminergic nerve terminals. J Neurochem 56 81 85. 

Staley JK, Talbot JZ, Ciliax BJ, Miller GW, Levey AI, Kung M-P, Kung HF, Mash DC (1997) Radioligand binding and immunoautoradiographic evidence for a lack of toxicity to dopaminergic nerve terminals in human cocaine overdose victims. Brain Res 747 219-229. 

An important neurotoxin, MPTP, is activated to MPP by MAO-B in the brain. The subsequent uptake of MPP into the mitochondria of dopaminergic nerve terminals depletes the cells of ATP by inhibiting oxidative phosphorylation. MAOs are also therapeutic targets. Since these enzymes deaminate neurotransmitters such as norepinephrine and... 

Recently, the development of " Tc-labcled tropane derivatives used as dopamine transporter imaging agents has been reported. The dopamine transporter is a protein complex located prcsynaptically at dopaminergic nerve terminals [247]. It is depleted in Parkinson s disease, and the extent of depletion correlates with the loss of dopamine [248], Among a series of tropane derivatives [249,250] labeled with " Tc, two compounds deserve more attention. 

L-dopa is a chemical intermediate produced in the synthesis of dopamine (see Figure below). It is formed from the actions of tyrosine hydroxylase on tyrosine, and is subsequently converted into dopamine by aromatic-L-amino acid decarboxylase (LAAD, or dopa decarboxylase). This molecule is taken up into the dopaminergic nerve terminal and converted to dopamine, which is then released into the synaptic cleft. Unlike dopamine, dopa is in nonionized form at physiologic pH and thus will cross into the central nervous system (CNS). 

Fig. 23.5. Schematic of a dopaminergic nerve terminal. Amphetamine increases synaptic concentration of dopamine primarily by causing its release from presynaptic terminals, whereas cocaine increases synaptic concentration by preventing its reuptake (a).

Levodopa is the immediate precursor of dopamine and is able to penetrate the brain, where it is converted to dopamine. The site of this decarboxylation in the parkinsonian brain is uncertain, but a.s dopa decarboxylase is not rate limiting, there may be. sufficient enzyme in the remaining dopaminergic nerve terminals. Another possibility is that the conversion occurs in noradrenergic or serotonergic terminals, because the decarboxylase activity in these neurotics is not specific. In any event, the release of dopamine replaced in the brain by Icvodopa therapy must be very abnormal, and it is remarkable that most patients with Parkinson s disease benefit, often dramatically, from its administration. 

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