Dopamine receptors

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3D structural model of the dopamine D 3 receptor with a bound ligand
Nerve cell with dopamine receptors marked in red

Dopamine receptors are the receiving unit for signals from the neurotransmitter dopamine . The receptor can be found on the cell surface, among other things, of special neurons and special smooth muscle cells of kidney vessels. Five different forms of the dopamine receptor are known today. In terms of quantity , D 1 and D 2 receptors represent the most common sub-forms. These differ in the different signal path (so-called second messenger ) from the receptor to the cell and in different pharmacological influences. The influence of so-called agonists or antagonists on dopamine receptors plays an important role in the treatment of Parkinson's disease , vomiting and in treatment with neuroleptics . Mutations in DRD2 - gene associated with alcoholism and myoclonic dystonia .

Grouping

Due to the different intracellular signaling pathways and effects, a distinction is made between two groups of dopamine receptors:

  1. D 1 / D 5 group (D 1 -like group for short ): When this group of receptors is stimulated by dopamine, the intracellular signal is first transmitted via a so-called stimulatory G protein . This activates the enzyme adenylate cyclase . The activated adenylate cyclase effects the conversion of intracellular ATP into cAMP (cyclic AMP). This in turn activates other intracellular proteins. The main purpose of this signal cascade is to amplify the signal emanating from a receptor, as several subsequent proteins are activated at each activation stage. This group thus has an activating effect on the cell.
  2. D 2 / D 3 / D 4 group (D 2 -like group for short ): When this group of receptors is stimulated by dopamine, the intracellular signal transmission first takes place via a so-called inhibitory , i.e. H. inhibitory G protein . This protein inhibits adenylate cyclase. As a result, less cAMP is produced and thus the subsequent signal path is inhibited. This group also activates potassium channels . This z. B. stabilizes the resting potential of nerve cells and excitation of a nerve cell is less likely. This group thus has an inhibitory effect on the cell.

Subforms of the dopamine receptor

structure

Dopamine receptors are proteins that are characterized by their central structural motif, the seven helices that span the cell membrane . This postulated structure could be confirmed for the D 3 receptor with the aid of the crystal structure analysis.

pharmacology

The different pharmacology of the following substances can be explained, among other things, by the different distribution of the substances in the brain across the blood-brain barrier . For example, infused dopamine does not reach the brain directly, while apomorphine mainly only reaches the area postrema . The area postrema is one of the so-called circumventricular organs . There is a break in the blood-brain barrier here.

  • Dopamine : When infused, dopamine mainly stimulates the D 1 receptors in the kidney and mesenteric vessels and thus initially increases the blood flow in the kidneys and intestines. At higher doses, there are also effects via adrenoceptors .
  • Apomorphine : Apomorphine activates D 2 receptors. Mainly used to compensate for the dopamine deficit in Parkinson's disease. Strong trigger of the nausea.
  • Bromocriptine : Bromocriptine activates the D 2 receptor. Used, among other things, in Parkinson's disease , for weaning (inhibits prolactin formation). Side effects include nausea and vomiting .
  • Metoclopramide and domperidone : Among other things, metoclopramide blocks the D 2 receptor in the area postrema and thus inhibits the induction of vomiting. Domperidone probably accelerates the stomach movement in the direction of the duodenum while inhibiting the D 2 receptor. Use of both substances as so-called anti - emetics in relapsed vomiting and as prokinetics .
  • Haloperidol , acepromazine and other neuroleptics: These predominantly inhibit the D 2 receptor (possibly also D 4 and D 3 ). Use for schizophrenia and agitation, among other things .
  • Clozapine : Clozapine is an atypical neuroleptic and mainly inhibits the D 4 receptor. It comes z. B. used in schizophrenia .
  • Pramipexole activates the D 3 receptors in the limbic system and in the frontal cortex.

literature

  • Larry Squire et al: Fundamental Neuroscience. Academic Press, London 2003, ISBN 0-12-660303-0 , p. 254.
  • Oliver von Bohlen, Halbach, Rolf Dermietzel: Neurotransmitters and Neuromodulators. Wiley-VCH, 2006, ISBN 3-527-31307-9 , pp. 59-74.

swell

  1. ↑ JN Joyce, MJ Millan: Dopamine D3 receptor agonists for protection and repair in Parkinson's disease . In: Current Opinion in Pharmacology . tape 7 , no. 1 , February 2007, p. 100-105 , doi : 10.1016 / j.coph.2006.11.004 , PMID 17174156 .
  2. ^ ME Breuer, L. Groenink, RS Oosting et al .: Antidepressant effects of pramipexole, a dopamine D3 / D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats . In: European Journal of Pharmacology . tape 616 , no. 1-3 , August 2009, pp. 134-140 , doi : 10.1016 / j.ejphar.2009.06.029 , PMID 19549514 .
  3. ↑ V. Bertaina-Anglade, CD La Rochelle, DK Scheller: Antidepressant properties of rotigotine in experimental models of depression . In: European Journal of Pharmacology . tape 548 , no. 1-3 , October 2006, pp. 106-114 , doi : 10.1016 / j.ejphar.2006.07.022 , PMID 16959244 .
  4. ↑ EY Chien, W. Liu, Q. Zhao, V. Katritch, GW Han, MA Hanson, L. Shi, AH Newman, JA Javitch, V. Cherezov, RC Stevens: Structure of the human dopamine D3 receptor in complex with a D2 / D3 selective antagonist. Retrieved November 15, 2010 .
  5. ↑ Pramipexole relieves depression in Parkinson's disease. In: Doctors newspaper online. January 11, 2005.