Dopamine exocytosis

D2-like receptors couple mainly to Gi/o proteins, as mentioned above. However, there is no direct evidence to support this coupling for the release-modulating autoreceptors. Moreover, the subsequent intracellular signal transduction has never been studied directly in axon terminals. Mouse AtT-20 pituitary cells, which release acetylcholine and adrenocorticotropic hormone, have been used as a model for axon terminals. When expressed in these cells, D3 receptors mediated inhibition of P/Q-type calcium channels and activation of G protein-coupled inward rectifier potassium channels (Kuzhikandathil et al. 1998 Kuzhikandathil and Oxford 1999). Both would explain the autoreceptor-mediated inhibition of dopamine exocytosis. 

C. Spegel, A. Heiskanen, J. Acklid, A. Wolff, R. Taboryski, J. Emneus and T. Ruzgas, On-chip determination of dopamine exocytosis using mercapto-propionic acid mothfied microelectrodes. Electroanalysis, 19(2-3), 263-271 (2007). 

H.F. Cui, J.S. Ye, Y. Chen, S.C. Chong, X. Liu, T.M. Lim and F.S. Sheu, In situ temporal detection of dopamine exocytosis from 1-dopa-incubated nm9d cells using microelectrode array-integrated biochip, Sensors and Actuators B-Chemical, 115(2), 634-641 (2006). 

Figure 17.1.6 Amperometric monitoring of repeated exocytosis events at artificial cells and cells. (A) Amperometric detection of continuous exocytosis of three vesicles from an artificial cell (scale bars are 40 pA and 3000 msec). (B) Amperometric detection of dopamine exocytosis from a PC12 cell (scale bars are 10 pA and 40 msec). (C) Plot of half-width vs. vesicle radius for vesicles fusing from an artificial cell where the vesicle radius has been the only parameter varied in the experiment. Reproduced with permission from (79).

Neurotransmitter Transporters. Figure 3 Dopamine turnover at a presynaptic nerve terminal, (a) Dopamine is produced by tyrosine hydroxylase (TH). When secretory vesicles are filled, they join the releasable pool of vesicles at the presynaptic membrane. Upon exocytosis, the diffusion of released dopamine is limited by reuptake via DAT. (b) If DAT is inactive, dopamine spreads in the cerebrospinal fluid but cannot accumulate in secretory vesicles. This results in a compensatory increase of dopamine hydroxylase activity and a higher extracellular dopamine level mice with inactive DAT are hyperactive. 

FIGURE 4-23 Experimental setup for monitoring dopamine release by exocytosis, from a cell body. The microelectrode and glass capillary (containing the chemical stimulant) are micromanipulated up to the cell body. (Reproduced with permission from reference 82.)... 

Cysteine string protein (CSP) Cytochrome b561 Peripheral membrane protein that is paimitoylated on >10 cysteines. May have a role in Ca2+ sensitivity of exocytosis. Electron-transport protein required for intravesicular monooxygenases in subsets of secretory vesicles. Required for dopamine- -hydroxylase and peptide amidase activity. 

In addition to releasing norepinephrine (through exocytosis), the stimulation of sympathetic neurons also releases ATP, storage protein, and dopamine P-hydroxylase. The released norepinephrine interacts with receptor sites located postsynaptically (a,) to produce the desired effects. 

A useful model of the action of these two drugs in the reward centers of the CNS is shown in Figure 32-1. Cocaine reduces reuptake of dopamine into the neuron by inhibiting the dopamine reuptake transporter. Amphetamine causes the intracellular release of dopamine within the terminal and reverses the transporter direction so that dopamine is released into the synapse by reverse transport rather than ordinary exocytosis. In addition, amphetamine inhibits intracellular MAO metabolism of dopamine. Note that both drugs result in an increase in the concentration of dopamine in the synapse. 

Monoaminergic neurotransmitters (dopamine, noradrenaline, adrenaline, histamine, and serotonin) are released by exocytosis of small dense-core vesicles from... 

Classical neurotransmitters and monoamines may rarely be secreted by neurons, not by exocytosis, but by transporter reversal. This mechanism involves the transport of neurotransmitters from the cytosol to the extracellular fluid via transporters that normally remove neurotransmitters from the extracellular fluid. This mechanism appears to account for the burst of dopamine released by amphetamines (Fleckenstein et al., 2007), but its physiological occurrence remains unclear. 

Wu LG, Betz WJ (1996) Nerve activity but not intracellular calcium determines the time course of endocytosis at the frog neuromuscular junction. Neuron 17 769-79 Zenisek D, Steyer JA, Feldman ME, Aimers W (2002) A membrane marker leaves synaptic vesicles in milliseconds after exocytosis in retinal bipolar cells. Neuron 35 1085-97 Zhou FM, Liang Y, Salas R, Zhang L, De Biasi M, Dani JA (2005) Corelease of dopamine and serotonin from striatal dopamine terminals. Neuron 46 65-74 Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64 355—405... 

Abstract Presynaptic receptors for dopamine, histamine and serotonin that are located on dopaminergic, histaminergic and sertonergic axon terminals, respectively, function as autoreceptors. Presynaptic receptors also occur as heteroreceptors on other axon terminals. Auto- and heteroreceptors mainly affect Ca2+-dependent exocytosis from the receptor-bearing nerve ending. Some additionally subserve other presynaptic functions. 

Our knowledge of presynaptic dopamine and serotonin receptors dates back to the 1970s (Famebo and Hamberger 1971). Presynaptic histamine receptors were discovered in 1983 (Arrang et al. 1983). Presynaptic dopamine receptors occur as autoreceptors, i.e., on dopaminergic axon terminals, and as heteroreceptors on nondopaminergic axon terminals. By analogy the same holds true for presynaptic histamine and serotonin receptors. The early days of the dopamine autoreceptors were stormy, but the controversies were finally solved (see Starke et al. 1989). The main function that presynaptic receptors affect is transmitter release, which in this article means Ca2+-dependent exocytosis. However, some receptors discussed in... 

A single neuron-like PC 12 cell was trapped in an etched glass (30 pm deep) pocket sealed against a PDMS channel layer (20 pm). Quantal release of dopamine (in transient exocytosis) from the cell as stimulated by nicotine was amper-ometrically detected with a carbon fiber electrode. The cells flow into the channels caused by the liquid pressure which was provided by a liquid height at the sample reservoir (e.g., 0.5-2 mm). To facilitate transport of cells in the microchannels, the cell density should not be higher than lOVmL. Serious cell adhesion occurred if the transport speed was low (as provided by liquid height below 0.5 mm),... 

The major regulator of catecholamine release from the adrenal medulla is cholinergic stimulation, which causes calcium-dependent exocytosis of the contents of the secretory granules. Exocytosis of the granular content releases epinephrine (E), NE, DA, dopamine -hydroxylase, ATP, peptides, and chromaffin-specific proteins that are biologically inert. The amounts of DA and NE released are minor in comparison with that of E. Of the total catecholamine content in the granules, approximately 80% is E, 16% is NE, and the remainder is mostly DA. 

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