The role of dopamine_Kain Industrial Additives

Background and overview^[1][2]

Dopamine is the main catecholamine neurotransmitter in the mammalian brain. It controls many functions such as movement, cognition, emotion, positive reinforcement, feeding, and endocrine regulation. The dopamine system has been one of the focuses of research in the past 30 years, with some diseases such as Parkinson’s disease, schizophrenia, and Tourette syndrome. Attention deficit hyperactivity syndrome and others are related to disorders of dopamine transmitter transmission.

Physical and chemical properties and structure^[1]

Dopamine is a catecholamine neurotransmitter. It is a single benzene ring group structure, that is, it consists of a catechol core (the benzene ring connects two hydroxyl groups) and an ethylamine or its derivative as a side chain. The precursor for the synthesis of dopamine is the aromatic amino acid tyrosine, which is converted into dopamine through two reactions. First, tyrosine hydroxylase (TH) catalyzes the synthesis of L-3,4-dihydroxyphenylalanine (z-DOPA) from tyrosine, and then aromatic amino acid decarboxylase further catalyzes DOPA to produce dopamine. Dopamine accounts for 80% of all catecholamine neurotransmitters in the brain. The brain areas that synthesize dopamine and their fiber projections form four pathways: (1) nigrostriatal tract; (2) mesolimbic tract; (3) mesocortical tract; (4) nodoinfundibular tract.

The fiber projections of the nigrostriatal pathway originate from dopaminergic neurons in the substantia nigra pars compacta (sNc) of the midbrain and innervate the dorsal striatum (caudate putamen). The nigrostriatal tract is involved in the control of movement, and its degeneration can cause Parkinson’s disease, which is characterized by tremors, rigidity, and reduced movements. The mesencephalic cortex originates from the ventral tegmental area (vTA) of the midbrain and controls a large area of ​​the prefrontal cortex. This pathway involves learning and memory. The mesolimbic tract originates from area VIA of the midbrain and innervates the ventral striatum (nucleus accumbens), olfactory tubercle (OT) and part of the limbic system. This pathway is associated with motivated behavior. The tuberoinfundibular tract originates from the arcuate nucleus of the hypothalamus and projects to the median eminence of the hypothalamus. It releases dopamine around the capillary plexus of the hypothalamic pituitary portal system, and is then transported to the anterior pituitary where it acts on prolactin cells to inhibit prolactin. of release.

dopamine

Dopamine receptor^[3]

Dopamine acts through its corresponding membrane receptor, which is a family of G protein-coupled receptors composed of seven transmembrane domains (7-GM). Five dopamine receptors (DA-R) have been isolated so far. According to their biochemical and pharmacological properties, they can be divided into D1 class and D2 class receptors. The D1 class of receptors includes D1 and D5 receptors (also called D1A and D1B receptors in rats). The D2 class of receptors includes D2, D3 and D4 receptors. The C-termini of both types of receptors contain phosphorylation and palmitoylation sites, which are involved in the desensitization process of agonist-dependent receptors and the formation of the fourth intracellular loop.

Dopamine ligand compounds readily distinguish the Dl receptor and D2 receptor families, but most compounds cannot distinguish between receptor subtypes of the same family. For example: D1 receptor antagonist scH_23390 or agonist sKF-38393 has the same affinity for D1 receptor and D5 receptor. Research on the pharmacological selectivity of dopamine ligand compounds is currently ongoing in many organisms. The use of animal models lacking a specific receptor will help clarify the selectivity of ligand compounds for each receptor.

Function^[2]

Dopamine and movement: Dopamine plays an important role in movement control. Parkinson’s disease is caused by the severe reduction of dopamine caused by the degeneration of dopaminergic neurons. Studies using dopamine antagonists and agonists have shown the important role of dopamine receptors in motor control such as forward, backward, freezing, inhalation and grooming functions in rats. Typically agonists increase dopamine’s motor function, and antagonists have the opposite effect. It is clear that the D1 and D2 receptors interact to promote each other in determining forward movement. Simultaneous stimulation of D1 receptors results in maximal locomotor stimulation with D2 receptor agonists.

Behavioral analysis of dopamine receptor (D14) mutant mice provides information on each locomotor subtype. Contrary to the results of pharmacological studies, the motor function of Dl-R mutant mice was not affected compared with wild-type mice, indicating the complexity of the interaction between different dopamine receptors in the regulation of voluntary movement. D2. R knockout mice showed obvious impairment of motor function, such as reduced movement, incoordination or inability to move backwards. D3-R mutant mice appearThe motor subtype of hyperactivity is consistent with the results of pharmacological administration of D3-R agonists or antagonists. The motor function of D4-R mutant mice is also affected.

Dopamine and drug addiction: The mesolimbic dopamine system is related to the psychomotor effects caused by drug addiction, including opiates, cocaine, amphetamines and ethanol, as well as the control of reward mechanisms. Cocaine and amphetamines increase dopamine release in the synaptic cleft by blocking the activity of the dopamine transporter (DAT) and flipping dopamine transport. However, opioids exert inhibitory effects on dopamine release in the striatum, prefrontal cortex, optic nerve, nucleus accumbens, medial hypothalamic nucleus, and amygdala.

Disruption of the nucleus accumbens, or blockade of dopamine receptors with D1 or D2-R antagonists, has been shown to attenuate the hyperkinesia and reward effects induced by morphine, cocaine, and amphetamines. In contrast, administration of D2 receptor agonists such as quinpimle and bromocriptine can mimic the effects of cocaine and can enhance the effects of cocaine if used in combination with cocaine. After Dl-R knockout mice were treated with cocaine, the classic hyperkinesia and stereotyped behavioral effects did not occur. In a place-selective experimental model, D2-R knockout mice lacked morphine-conditioned reflexes compared with wild-type mice. D3-R mutant mice have increased sensitivity to cocaine. D4-R mutant mice are more sensitive to stimulation of locomotor activity induced by ethanol, cocaine, and amphetamines.

Main reference materials

[1] Xia Chunhe, Chen Liping, Xu Jing, Wang Qiaoling, Deng Wenlin, & Yan Chunxiang. (2001). Effects of intravenous injection of dopamine and dobutamine on peripheral veins and surrounding tissues of young rabbits. Chinese Journal of Nursing , 36(11), 805-807.

[2] Xu Youyi, Jiang Jinhong, Zhu Liping, & Zhu Baoku. (2011). Self-polymerization-adhesion behavior of dopamine and membrane surface functionalization. Membrane Science and Technology, 31(3), 32-38.

[3] Mihrigul, Wumuhasim, & Annivar Kurban. (2013). Clinical observation of sodium nitroprusside combined with dopamine in the treatment of heart failure. Chinese Journal of Circulation, 28(3 ).