DOPAMIN.

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1 DOPAMIN

2 A dopaminerg neurotranszmisszio egyszeru semaja

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4 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.

5 A dopamin receptorok szignaltranszdukcioja

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

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8 Dopamin metabolitok Agytörzsi magvak Limbikus kéreg HOMOVANILINSAV:
Nigro-striatalis pályák! HOMOVANILINSAV: Szintje a dopaminerg neuronok funkcionális állapotara utal Parkinson kór â Schizophrenia á

9 A dopaminerg rendszer kóros működése következtében kialakuló betegségek:
Parkinson kór Schizophrenia

10 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.

11 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)

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13 A Parkinson kor terapiaja
*L-DOPA (levodopa) Periferiás DOPA-dekarboxiláz aktivitas à1 % kerül az agyba Kombináció:Carbidopa (DOPA-dekarboxiláz gátló, agy-vér gáton nem jut át, csak a periferian gatol) * Dopamin receptor agonisták (schizophrenia!)

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15 Schizophrenia Egyik elképzelés: Hatékony antipsychotikus szerek:
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

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

17 Some properties of dopamine receptors
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 catecholamine family 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.

18 Some, at least, are regulated by phosphorylation.
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.