Dopamine: Receptors, Functions, Synthesis, Pathways, Locations and Mental Disorders: Review of Literatures

Abstract

Dopamine is monoamine neurotransmitter. Dopamine is produced in the dopaminergic neurons in the ventral tegmental area of the substantia nigra, midbrain and the arcuate nucleus of the hypothalamus. In the periphery, dopamine is found in the kidney where it functions to produce renal vasodilation, diuresis, and natriuresis. Dopamine neurons are more widely distributed than those of other monamines and it is found in hypothalamus, olfactory bulb, the midbrain substantia nigra and ventral tegmental area and in the periaqueductal gray and retina. There are five subtypes of dopamine receptors, D1, D2, D3, D4, and D5, which are members of the large G-protein coupled receptor super family. The dopamine receptor subtypes are divided into two major subclasses: types 1 and 5 are similar in structure and drug sensitivity, and these two receptors are referred to as the "D1like" group or class of receptors. Dopamine receptor types 2, 3, and 4 are called the "D2like" group. Dopamine plays central role in pleasurable reward behavior, inhibition of prolactin production (involved in lactation), sleep, mood, attention, learning, behavior, control of nausea and vomiting and pain processing. In addition it also involved in controlling movement, emotion and cognition. Due to extensive localization of dopamine receptor to brain areas and its role in wide range of functions, dopaminergic dysfunction has been implicated in the pathophysiology of schizophrenia, mood disorders, obsessive compulsive disorder (OCD), autism spectrum disorders, attention deficit-hyperactivity disorder (ADHD), tourette's syndrome, substance dependency, Parkinson's disease and other disorders. the D 2 receptor, implicating this subtype as an important site of antipsychotic drug action [3,4]. D 1 receptor has high affinity for the antagonist SCH 23390 and relatively low affinity for butyrophenones such as haloperidol. D 1 receptor activation stimulates cyclic adenosine monophosphate (cAMP) formation, D 2 receptor stimulation produces the opposite effect. In addition to the stimulation of adenylate cyclase, D 1 receptors may also stimulate phosphoinositide turnover and modulate intracellular calcium levels [1,3]. The D1 receptors are found in high concentration in the hypocampus, caudate, putamen, nucleus accumbens, hypothalamus, substantia nigra pars reticulata, olfactory tubercle and frontal and temporal cortex [3,5]. D 1 receptors have been implicated in the cognitive functions of dopamine such as the control of working memory and attention. D 1 receptors contribute significantly to the CNS effects of cocaine, suggesting the involvement of other receptors in addition to the D 2 receptor, in mediating rewarding effects of drugs of abuse [1,3,5]. D1 and D5 receptors have a higher degree of homology with each other than with the D 2-4 subtypes. D5 receptor has 50% homology which are members of the large G-protein coupled receptor super family [1]. The dopamine receptor subtypes are divided into two major subclasses: types 1 and 5 are similar in structure and drug sensitivity, and these two receptors are referred to as the "D1like" group or class of receptors. Dopamine receptor types 2, 3, and 4 are also similar in structure and are, therefore, grouped together as the "D2like" group [2]. Dopamine receptors are typically couple to G s and G i mediated transduction systems [3]. The ultimate effect of D1-like activation (D1 and D5) can be excitation (via opening of sodium channels) or inhibition (via opening of potassium channels); the ultimate effect of D2-like activation (D2, D3, and D4) is usually inhibition of the target neuron [2]. The effect of dopamine on a target neuron depends on which types of receptors are present on the membrane of that neuron and on the internal responses of that neuron to the second messenger cAMP [2]. D1 receptors are the most numerous dopamine receptors in the human nervous system and D2 receptors are the second most abundant receptors. D3, D4, and D5 receptors are present at significantly lower levels [2]. D1 and D5 receptors mostly involved in post synaptic inhibition. D2, D3, and D4 receptors are involved in both pre-and postsynaptic inhibition. D2 receptors regulates mood, emotional stability in the limbic system and movement control in the basal ganglia [3,4]. D 1 and D 2 receptors were distinguished on the basis of differential binding affinities of a series of agonists and antagonists, distinct effectors mechanisms, and distinct distribution patterns within the CNS. It was subsequently found that the therapeutic efficacy of antipsychotic drugs correlated strongly with their affinities for