Dopamine receptors characteristics

These symptoms are alleviated by administering levodopa (L-dopa), a precursor for dopamine. L-dopa is taken up by the axon terminals of dopaminergic neurons and used to form dopamine. Interestingly, in some patients, a side effect of dopamine replacement therapy is the development of symptoms characteristic of schizophrenia. (Recall that this mental disorder is caused by overactive dopaminergic neurons.) On the other hand, drugs used to treat schizophrenia — dopamine receptor antagonists — may elicit symptoms of Parkinson s disease. 

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. 

At this point in time the pharmacological characteristics of the functionally different dopamine receptors, present in the neostriatum, can (still) be described in terms of D-1 and D-2 receptors there is (still) no need to assume the presence of D-3 or D-4 receptors to explain the biochemical and physiological responses elicited by dopamine. It is conceivable... 

In our model, we have indicated that atypical antipsychotics (12) (sulpiride, metoclopramide, molindone, and Ro 22-1319) differ from classical neuroleptics (tricyclics, butyrophenones, butaclamol, diphenyl-piperidines) by lacking a lipophilic functional group on the basic nitrogen that could extend into the auxiliary binding site identified in our model. The absence of this lipophilic functionality may now be stated to be the characteristic which distinguishes selective D-2 dopamine receptor antagonists from non-selective antagonists. 

Hietala J, West C, Syvalahti E, Nagren K, Lehikoinen P, Sonninen P, Ruotsalainen U (1994) Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence. Psychopharmacology 776 285-290. 

On the basis of structural, pharmacological, functional and distributional similarities, all dopamine receptor subtypes fall into one of the two initially recognised receptor categories, here designated dopamine D,- or dopamine D2-like receptors. Dopamine D5 receptors share extensive similarities with dopamine D, receptors, while dopamine D3 and D4 receptors more closely conform to the features of dopamine D2 receptors. The properties of the two subfamilies closely resemble those of the dopamine D, and D2 receptor subtypes as originally defined by Kebabian and Caine.9 The most important characteristics of the cloned human dopamine receptor subtypes are summarised in Table 1.1. 

Table 1.1 Summary of the characteristics of cloned human dopamine receptor subtypes.

Ritchie T, Noble EP (2003) Association of seven polymorphisms of the D2 dopamine receptor gene with brain receptor-binding characteristics. Neurochem Res 28 73-82... 

Dopamine receptors (Dj and D2) have a greater affinity for DA than for NE or E (Table 32-3). Both subtypes exert effects by altering the activity of adenylate cyclase via a G-protein. Di receptors coupled to Gsa activate the enzyme and cause a rise in intracellular cyclic AMP. D2 receptors are coupled to G i, and inhibit the enzyme (Table 32-3). At very high concentrations, however, dopamine is capable of activating a-adrenergic receptors, which results in an effect resembling that of NE (vasoconstriction) instead of the characteristic vasodilatation elicited by low concentrations of DA. 

The characteristics of one of the antibodies in the structure-activity relationships of binding haloperidol analogs was quite close to what is accepted as a reasonable pharmacophore map for the dopamine receptor ... 

Parkinson s disease was the first neurological disorder to be associated with deficiency of a specific neurotransmitter. In Parkinson s disease, there is a deficiency of dopamine in the basal nuclei, which leads to overactivity of cholinergic pathways and the characteristic hypokinesia, rigidity and tremor. Drugs used to treat Parkinson s disease aim to replace dopamine stimulate dopamine receptors or the release of remaining dopamine reduce breakdown of dopamine or reduce excessive parasympathetic activity. More recently, attempts have been made to replace dopamine-secreting cells by transplantation of fetal brain tssue. 

FIGURE 20-4 Distribution and characteristics of dopamine receptors in the central nervous system. SNpc, sub-stantia nigra pars compacta. 

Somatostatin and dopamine are two major neurotransmitter systems that share a number of structmal and functional characteristics. Somatostatin receptors and dopamine receptors are co localized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. The molecular basis for such interaction between the two systems is unclear. It was shown that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-ohgomerization to create a novel recep-... 

Dopamine receptors were originally subdivided into two types (D, and Dj). Currently there are live cloned dopamine receptors that fall into these two classes, llte D -like receptors include D, and D,. while the D -like receptors include D,. Dj and D, The dopamine recepiors all display the seven transmembrane-spanning domains characteristic of G-protein-linked receptors and are linked to adenylyi cycla.se stimulation (Dj) or inhibition (D,). 

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