Dopamin
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DOPAMIN. A dopaminerg neurotranszmisszio egyszeru semaja. A dopaminerg axon terminalis.

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DOPAMIN

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Dopamin

DOPAMIN


A dopaminerg neurotranszmisszio egyszeru semaja

A dopaminerg neurotranszmisszio egyszeru semaja


A dopaminerg axon terminalis

A dopaminerg axon terminalis

Left picture shows rich presence of dopamine-containing nerve endings (green dots) in the basal ganglia of a rat brain, visualized by fluorescence microscopy. To the right, a close-up of one nerve ending as seen in the electron microscope. The black dots in the vesicles represent stored dopamine.


A d opamin receptorok szignaltranszdukcioja

A dopamin receptorok szignaltranszdukcioja


Az adenil cikl z t befolyasolo dopamin receptorok d 1 d 5 d 2

Az adenil-ciklázt befolyasolo dopamin receptorok (D1, D5, D2)


Dopamin m e tabolitok

Dopamin metabolitok

Agytörzsi magvak

Limbikus kéreg

Nigro-striatalis pályák!

HOMOVANILINSAV:

Szintje a dopaminerg neuronok funkcionális állapotara utal

Parkinson kór â

Schizophrenia á


A dopaminerg rendszer k ros m k d se k vetkezt ben kialakul betegs gek

A dopaminerg rendszer kóros működése következtében kialakuló betegségek:

Parkinson kór

Schizophrenia


Dopamin

Dopaminergic pathways of the human brain in normal condition (left) and Parkinson's disease (right). Red Arrows indicate suppression of the target, blue arrows indicate stimulation of target structure.


A parkinson k r indukalasa

A Parkinson kór indukalasa

*Cycad tree - trópusi gyom

B-N-metil-amino-alanin (BMAA)

*1-metil-4-phenyl-1,2,3,3-tetrahidropiridin (MPTP)

iv. kábítószerrel

(heroin-származék szintézise során keletkezik)

A dopaminerg neuronok felveszik

↓MAO-B

1-metil-4-fenil pyridinium (MPP+) → toxikus

*Complex I gatlok – (peszticidek, rotenon)


A parkinson kor terapiaja

A Parkinson kor terapiaja

*L-DOPA (levodopa)

Periferiás DOPA-dekarboxiláz aktivitasà1 % kerül az agyba

Kombináció:Carbidopa (DOPA-dekarboxiláz gátló, agy-vér gáton nem jut át, csak a periferian gatol)

* Dopamin receptor agonisták

(schizophrenia!)


Schizophrenia

Schizophrenia

Egyik elképzelés:

Centrális dopaminerg neuronok fokozott aktivitása

Hatékony antipsychotikus szerek:

Dopamin receptor gátlók – D2 receptor gatlo neuroleptikumok

(Parkinson kór alakulhat ki!)

  • Dopamin szint az agyban emelkedett

  • Homovanilinsav szint a liquorban emelkedett

  • D2 receptorok száma megnőtt

    USA lakosság 1 %-a érintett

    Kórházi ágyak 25 %-at ilyen betegek foglalják el


Dopamin

Some properties of dopamine receptors. New receptors, isolated using appropriate probes and genomic or cDNA libraries, are being reported frequently

  • At least five different major classes are recognized (D1-D5), with some subtypes formed by alternative splicing.

  • They are membrane proteins, at least some of which are glycosylated.

  • Most have seven transmembrane domains with cytoplasmic loops.

  • Most appear to be coupled to G proteins.

  • Some are positively coupled to adenylyl cyclase (eg, D1),

  • at least one (D2) negatively.

  • At least one subtype (of D1) appears to be coupled to phospholipase C.


Dopamin

Some properties of dopamine receptors. New receptors, isolated using appropriate probes and genomic or cDNA libraries, are being reported frequently

  • Five distinct subtypes of the D4 receptor have been recognized, it being the first member of the catecholaminefamily of receptors to show polymorphic variation in the human population.

    Based on

    Strange PG: Interesting times for dopamine receptors. Trends Neurol Sci 1991;14:43, and Iversen L: Which D4 do you have? Nature 1992;358:109.


Dopamin

Some properties of dopamine receptors. New receptors, isolated using appropriate probes and genomic or cDNA libraries, are being reported frequently

  • Some, at least, are regulated by phosphorylation.

  • Drug affinities of most neuroleptics for the D2 receptor reflect their potencies in treating schizophrenia.

  • The various receptors show different anatomic distributions.

  • The D4 receptor binds the atypical neuroleptic clozapine with an affinity ten times higher than that of D2 sites.


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