Dopamine receptor presynaptic

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... 

Presynaptic dopamine receptors modulate the release of a variety of neurotransmitters. When looking at Table 1 one may be impressed by the number of studies and the number of neuron systems studied. It is clear that, overall, Di-like presynaptic receptors are facilitatory, whereas D2-like presynaptic receptors are inhibitory in the case of the few exceptions, the reason often remains unclear. 

Table 1 Tissues in which neurotransmitter release is increased (f) or decreased (J.) by presynaptic dopamine receptor activation. Receptor classification (except with superscript11) as by the authors cited. Designation as D -like or D2-like where no differentiation between D and D5, or between D2, D3 and D4, was made...

Presynaptic histamine receptors are more uniform than presynaptic dopamine receptors. Only one type, H3, has been identified with certainty. Like presynaptic dopamine receptors, presynaptic H3 receptors occur as auto- and heteroreceptors... 

If presynaptic histamine receptors are more uniform than presynaptic dopamine receptors, the contrary holds true for presynaptic serotonin receptors they are even more diverse than presynaptic dopamine receptors. As mentioned in the Introduction, presynaptic 5-HT3 receptors, being ligand-gated ion channels, are covered in the chapter by Dorostkar and Boehm and will be mentioned here only occasionally. Presynaptic G protein-coupled 5-HT receptors inhibit the release of serotonin from serotonergic axon terminals and inhibit or enhance the release of other neurotransmitters (Table 4). 

Mizuno T, Schmauss C, Rayport S (2007) Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens. BMC Neurosci 8 8-23... 

Morgadinho MT, Fontes Ribeiro CA, Macedo TR (1999) Presynaptic dopamine receptors involved in the inhibition of noradrenaline and dopamine release in the human gastric and uterine arteries. Fundam Clin Pharmacol 13 662-70... 

Grossman F, Potter WZ, Brown EA, Maislin G (1999) A double-blind study comparing idazoxan and bupropion in bipolar depressed patients. J Affect Disord 56 237 13 Hamed AT, Jandhyala BS, Ginos JZ, Lockhandwala MF (1981) Presynaptic dopamine receptors and a-adrenoceptors as mediators of the bradychardic action of N-n-propyl-N-n-butyl dopamine. Eur J Pharmacol 74 83-90... 

Activation of neostriatal tyrosine hydroxylase was observed when cyclic AMP was added to high speed supernatants from rat neostriatum (133). Intraventricular injection of dibutyryl cyclic AMP stimulated tyrosine hydroxylation in the neostriatum (134). However, it is still questionable if under physiological conditions this cyclic AMP involvement in the feedback control of tyrosine hydroxylase activity is mediated by presynaptic dopamine receptors or by presynaptic allo-receptors. In addition, if a dopamine sensitive adenylate cyclase is involved in the regulation of neostriatal tyrosine hydroxylase activity it is relevant to know if this adenylate cyclase is linked to a D-1 and/or a D-2 receptor. At this point in time experimental data are not in favour of the presence of a D-l receptor linked to an adeiylate cyclase on the varicosities of dopaminergic neurons in the neostriatum. E.g. concentrations of dopamine agonists stimulating cyclic AMP formation inhibit tyrosine... 

Sofar (presynaptic) dopamine receptors mediating inhibition of dopamine turnover and/or release seem to display features resembling those of the D-2 receptor. However inconsistencies reported could finally lead to a subdivision of D-2 receptors in the near future or it will appear that some in vitro experimental conditions have been too extreme, which by itself would have induced changes in the pharmacological characteristic of the receptor. One obvious question emerging from this review is whether all D-2 dopamine receptors in the neostriatum are linked to an adenylate cyclase. With the methodology presently available it will be hopefully only a matter of time to answer this question. 

Another important property of dopamine is its ability to inhibit sympathetic nerve function by interacting with presynaptic dopaminergic receptors to decrease norepinephrine release (10). These receptors are not adenylate cyclase coupled and have been classified as D-2 (8). Activation of cardiac presynaptic dopamine receptors causes bradycardia, and of vascular presynaptic dopamine receptors passive vasodilation, the magnitude of which will depend on the contribution of adrenergic activity to maintaining heart rate and vascular smooth muscle tone (11,12). 

At high doses (R)-(92) selectively stimulated presynaptic dopaminergic receptor sites, whereas at lower doses it selectively stimulated postsynaptic receptor sites (59). In contrast, the ( S)-enantiomer stimulated presynaptic dopamine receptors and at the same dose level, it blocked postsynaptic dopamine recep-... 

Eighteen chronic schizophrenic patients receiving subcutaneous doses of apomorphine (a dopamine receptor agonist) and of placebo, in separate trials, showed significant improvement in psychotic symptoms after apomorphine. The results were interpreted in terms of the activation of presynaptic dopamine receptors by apomorphine, with a subsequent decrease in dopamine-mediated neural transmission. " The neuropsychotropic activity and toxicity of the oxidation products of apomorphine have been described. ... 

The presynaptic dopamine receptor antagonist (-)-OSU6162 has been labeled with and... 

Psychostimulants. Figure 2 Dopamine molecules have two different possible targets. Both ways are initially increased by DAT inhibition caused by methylphenidate pre- and postsynaptic dopamine receptors. Stimulation of postsynaptic receptors results in inhibition of presynaptic action potential generation. On the other hand, presynaptic receptor stimulation leads to a transmission inhibition of action potentials. Therefore, both mechanisms are responsible for a decrease in vesicular depletion of dopamine into the synaptic cleft (adapted from [2]). 

Markstein, R., and Lahaye, D. In vitro effect of the racemic mixture and the (-)enantiomer of N-n-propyl-3(3-hydroxyphenyl)-piperidine (3-PPP) on postsynaptic dopamine receptors and on a presynaptic dopamine autoreceptor. J. Neural Transm 58 43-53, 1983. 

Govindaiah G., Cox C. (2006). Depression of retinogeniculate synaptic transmission by presynaptic D(2)-like dopamine receptors in rat lateral geniculate nucleus. Eur. J. Neurosci. 23, 423-34. 

Wonnacott, S., Kaiser, S., Mogg, A., Soliakov, L., Jones, I.W. Presynaptic nicotinic receptors modulating dopamine release in the rat striatum. Eur. J. Pharmacol. 393 51, 2000. 

Giorguieff-Chesselet MF, Kernel ML, Wandscheer D, Glowinski J (1979) Regulation of dopamine release by presynaptic nicotinic receptors in rat striatal slices effect of nicotine in a low concentration. Life Sci 25 1257-1262... 

There is still some controversy over the precise anatomical location of the dopamine receptor subtypes, but there is now evidence that the D2 receptors are located presynaptically on the corticostriatal neurons and postsynaptically in the striatum and substantia nigra. Conversely, the receptors are found presynaptically on nigrostriatal neurons, and postsynaptically in the cortex. It is possible to differentiate these receptor types on the basis of their agonist and antagonist affinities. 

Mechanism of Action A tricyclic antidepressant that blocks the reuptake of neu-rotransmitfers, such as norepinephrine and serotonin, at CNS presynaptic membranes, increasing their availability at postsynaptic receptor sites. The metabolite, 7-OH-amoxapine has significant dopamine receptor blocking activity similarto halo-peridol. Therapeutic Effect Produces antidepressant effects. 

In addition to the effects on seretonin, buspirone demonstrates moderate affinity for presynaptic dopamine D2 receptors (Hiner et ah, 1988 Hardman et al., 1996 Chouinard et ah, 1999). The effect on the D2 receptors allows buspirone to reverse neuroleptic-induced catalepsy (Cole and Yonkers, 1995 Baldessarini, 1996). The clinical significance of the action of buspirone on the Dj autoreceptors is unknown (Jann, 1988). 

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