Thursday, May 25, 2017

Creative Enzymes Introduces the Molecular Basis of Dopamine for Anti-inflammatory: cAMP

Dopamine is a classic central neurotransmitter, which is synthesized by dopaminergic neurons and stored in vesicles, and may be released from neurons by cell cleavage. Dopamine acts on the dopamine receptor, and changes the cell membrane on the ion permeability through a series of reactions, resulting in physiological effects. Dopamine has the effect of regulating physical activity, mental activity, endocrine and cardiovascular activity. Dopaminergic neuronal lesions can lead to a variety of diseases, such as Parkinson's disease, schizophrenia and so on.

By the fifties, dopamine had been thought to be a precursor of synthetic norepinephrine. A team of pioneering studies confirmed that dopamine was an important neurotransmitter in the brain and that there was a close relationship with Parkinson's disease. Since then, scientists had conducted a lot of researches on dopamine, and people had deepen understanding on such magical small molecules.

It is now generally accepted that dopamine receptors have two subtypes: D1 and D2. In addition, the high affinity binding state of the D1 receptor is referred to as D3 and the D4 receptor is another binding state of the D2 receptor. It is generally believed that activation of the D1 receptor enhances adenylate cyclase activity and activation of D2 receptor inhibits the activity of adenylate cyclase. After D1 receptor excitatory, adenylate cyclase configuration changes. That is, inactive type forms into active type. The latter catalyzes ATP to form cAMP, thereby activating cAMP-dependent protein kinases. This protein kinase A (PKA) catalyzes the phosphorylation of protein I, to changes the permeability of the membrane to the ions, and regulate the activity of the biosynthetic enzyme or causes other effects. Phosphodiesterase and protein phosphatase I can respectively lead cAMP decomposition and acidification of the protein to dephosphoric acid, thus terminating DA effect.

Recently, scholars found that dopamine can pass through the D1 receptor, promoting the intracellular cAMP levels, inhibiting inflammatory body, and playing anti-inflammatory effect.

D2 receptor gene knockout animals showed significant central nervous system inflammatory response, indicating that dopamine may have a function against inflammation. And the patients lack of DA prone to have central nervous system inflammation and Parkinson's disease.

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