Vous êtes sur la page 1sur 27

DOPAMIN

Nur Fadhillah Khalid


(P062181024)
MATA KULIAH : NEURONTRASMITTER
DOSEN: Yulia Yusrini Djabir,S.Si,MBM.Sc,M.Si,Ph.D,Apt
DEFENITION

• Dopamine is a neurotrasmitter, synthesized from the amino acid tyrosine,


which is taken up into the brain via an active transport mechanism. Tyrosine is
produced in the liver from phenylalanine through the action of phenylalanine
hydroxylase. Tyrosine is then transported to dopamine containing neurons
where a series of reactions convert it to dopamine
BIOSYNTHESIS & RECEPTOR ACTIONS OF DOPAMINE
• Within catecholaminergic neurons, tyrosine hydroxylase catalyzes the
addition of a hydroxyl group to the meta position of tyrosine, yielding L-dopa.
This rate-limiting step in catecholamine synthesis is subject to inhibition by
high levels of catecholamines (endproduct inhibition). Because tyrosine
hydroxylase is normally saturated with substrate, manipulation of tyrosine
levels does not readily impact the rate of catecholamine synthesis.
• Once formed, L-dopa is rapidly converted to dopamine by dopa
decarboxylase, which is located in the cytoplasm.
• is now recognized that this enzyme acts not only on L-dopa but also on all
naturally occurring aromatic L-amino acids, including tryptophan, and thus it
is more properly termed aromatic amino acid decarboxylase
DOPAMINE RECEPTORS

• Are classified into the D1- and D2-like receptor subtypes (based on their molecular
structure and pharmacology
• D1-like receptors, composed of D1 and D5 receptors, stimulate adenylyl cyclase
activity,
• D2like receptors, composed of D2,D 3, and D4 receptors, inhibit adenylyl cyclase
activity and regulate/modulate the activity of several ion channels.
• In the early 1970s, receptors for neurotransmitters acting via second messengers had not been identified
biochemically nor were there definitive links to such messengers. The discovery by John W. Kebabian and Paul
Greengard of a dopamine-sensitive adenyl cyclase, accordingly, was a giant step forward. The investigators first
characterized the enzyme in sympathetic ganglia where in dopamine producing cells link pre- and post-synaptic
neurons. Then, in the corpus striatum, the brain area enriched in dopamine, they delineated the enzyme’s
properties and showed that it was inhibited by antipsychoticdrugs, leading to a large body of research on dopamine
as a mediator of antipsychotic drug action and putative roles for this transmitter in the pathophysiology of
schizophrenia.
THERE ARE FOUR MAJOR PATHWAYS FOR THE
DOPAMINERGIC SYSTEM IN THE BRAIN:

1. The Nigro-Stiatal Pathway


2. The Mesolimbic Pathway
3. The Mesocortical Pathway
4. The Tuberoinfundibular Pathway
1. THE NIGRO-STIATAL PATHWAY

• In which fibres originate from the substantia nigra (pars compacta) and project
rostrally to become widely distributed in the basal ganglia (caudate nucleus and
the putamen). In this pathway dopamine plays a significant role in movement
(the control of motor function and in learning new motor skills). Degeneration of
the nigrostriatal system causes Parkinson's disease.
• The extrapyramidal effects of antipsychotic drugs are thought to result from the
blockade of these striatal dopamine receptors .
2. THE MESOLIMBIC PATHWAY

• Where the dopaminergic projections originate in the ventral tegmental area,


and then spread to the amygdala, pyriform cortex, lateral septal nuclei and
the nucleus accumbens.
• In this pathway dopamine functions in emotion and reward systems.
Mesolimbic dopamine mediates pleasure in the brain. It is released during
pleasurable situations and stimulates one to seek out the pleasurable activity
or occupation.
• This means food, sex, and several drugs of abuse are also stimulants of
dopamine release in the brain, particularly in areas such as the nucleus
accumbens and prefrontal cortex.
• Antipsychotic drugs that decrease positive symptoms of schizophrenia by
blocking dopamine receptors in the mesolimbic pathway
3. THE MESOCORTICAL PATHWAY,

• In which the dopaminergic fibers also arise from the A10 region (the ventral
tegmental area) and project to the frontal cortex and septohippocampal regions.
• Mesocortical dopamine mediates cognitive and emotional behaviour.
• Levels of dopamine in the brain, especially the prefrontal cortex, help in improved
working memory and attentions.
• However, this is a delicate balance and as levels increase or decrease to abnormal
levels, memory suffers. Antipsychotic drugs worsen negative symptoms of
schizophrenia by blocking dopamine receptors in the mesocortical pathway
4. THE TUBEROINFUNDIBULAR PATHWAY

• which originates in the arcuate nucleus ofthe hypothalamus (arcuate and


paraventricular nuclei) and projects to pituitary gland (the median eminence).
• Dopamine in this pathway inhibit prolactin release. Antipsychotic drugs that
block dopamine receptors in the pituitary may thus disinhibit prolactin release
and cause galactorrhea.
• Dopamine is the main neuroendocrine inhibitor of the secretion of prolactin
from the anterior pituitary gland.
• Dopamine is occasionally called prolactin-inhibiting factor (PIF), prolactin-
inhibiting hormone (PIH), or prolactostatin
• Dopamine became clinically relevant when Hornykiewicz discovered its depletion in the caudate
nucleus of patients with Parkinson’s disease, whereas i.v. administration of L-dihydroxyphenylalanine,
the amino acid precursor of dopamine, dramatically and rapidly alleviated Parkinsonian symptoms
• Neurotransmitter yang berperan dalam patofisiologinya adalah DA, 5HT, Glutamat,
peptide,norepinefrin (Price, 2006).
• Pada pasien skizoprenia terjadi hipereaktivitas system dopaminergik (hiperdopaminergia
pada sistem mesolimbik →berkaitan dengan gejala positif, dan hipodopaminergia pada
sistem mesocortis dan nigrostriatal→bertanggungjawab terhadap gejala negatif dan gejala
ekstrapiramidal)
• Reseptor dopamine yang terlibat adalah reseptor dopamine-2(D2) yang akan dijumpai
peningkatan densitas reseptor D2 pada jaringan otak pasien skizoprenia.
• Peningkatan aktivitas sistem dopaminergik pada sistem mesolimbik yang bertanggungjawab
terhadap gejala positif. Sedangkan peningkatan aktivitas serotonergik akan menurunkan
aktivitas dopaminergik pada sistem mesocortis yang bertanggung-jawab terhadap gejala
negatif.
CONCLUSION

1. Neurontrasmitter Dopamin memiliki prekursor yang sama dengan epinefrin dan norepinefrin yaitu L-
Thyrosin yang berasal dari hati.
2. Memiliki 2 tipe reseptor, D1 like reseptor & D2 like reseptor
3. Tubuh dapat optimal fungsinya bila terjadi keseimbangan neurontransmitter
4. Efek buruk dapat terjadi apabila produksi dopamin menurun seperti pada pasein parkinson yakni
terdapat defek pada substansia nigra sehingga aktivitas motoriknya mengalami gangguan.
5. Pada kondisi schizophrenia apabila kadar dopamin meningkat akan mengakibatkan timbulnya gejala
postif dan sebaliknya apabila kadar dopamin menurun akan mengakibatkan timbulnya gejala negatif.
REFERENCE
1. Ayano .Dopamine: Receptors, Functions, Synthesis, Pathways, Locations and Mental Disorders: Review
of Literatures. and Treatment. Journal of Mental Disorders and Treatment .2016. Volume 2 • Issue 2
2. Chunyu Zeng, Pedro A. Jos. Dopamine Receptors .Important Antihypertensive Counterbalance Against
Hypertensive Factors. AHAJournals. (Hypertension. 2013 ;57:11-17.)
3. Blum ,et al. Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and
AddictionJournal of Reward Deficiency Syndrome . 2015. Volume 1 Issue 3.
4. Solomon H. Snyder. What dopamine does in the brain. November 22, 2011. vol. 108 no. 47 , 18869–
18871
5. Philip,G. Dopamine receptor. Tocrics review. No.30 2008: UK
6. Charles A. Marsden. Dopamine: the rewarding years. British Journal of Pharmacology (2006) 147,
S136–S144

Vous aimerez peut-être aussi