Bioinformatics Research Laboratory, IBI Biosolutions Pvt. Ltd. India
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The DB-DRD4
Database Project |
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Dopamine receptors
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.Dopamine receptors have key roles in many processes, including the control of motivation, learning, and fine motor movement, as well as modulation of neuroendocrine signaling. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders. Thus, dopamine receptors are common neurologic drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors.
There are five types of dopamine receptor - D1, D2, D3, D4 and D5, and their variants.The D1 and D5 receptors are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 receptors are members of the D2-like family. There is also some evidence that suggests the existence of possible D6 and D7 dopamine receptors, but such receptors have not been conclusively identified.
These five subtypes of dopamine receptor have been cloned. The D1 and D5 receptors are closely related, and couple to Gsalpha and stimulate adenylyl cyclase activity. In contrast, the D2, D3 and D4 receptors couple to Gialpha and inhibit the formation of cAMP. SKF-38393 is a selective D1/D5 agonist. D1 receptors are found within the neostriatum, nucleus accumbens and substantia nigra. SCH-23390 is a potent D1 antagonist.
D2 receptors are found in the pituitary, striatum, limbic system and the substantia nigra. Both bromocriptine and apomorphine mimic the action of dopamine at D2 receptors. Dopamine receptors are involved in neurological disorders such as Parkinson's disease and schizophrenia. The ability for a group of chemically unrelated compounds to act as sedatives and thus provide treatment for schizophrenia has been attributed to their ability to block dopamine receptors.
Dopamine Receptors D1 D2 D3 D4 D5 Antagonists SCH-23390 - - - SCH-23390 Agonists SKF-38393 - - - SKF-38393 G protein Gαs Gαi/o Gαi/o Gαi/o Gαs Intracellular response Adenylyl cyclase stimulation Adenylyl cyclase inhibition Adenylyl cyclase inhibition Adenylyl cyclase inhibition Adenylyl cyclase stimulation
D1-like family
Activation of D1-like family receptors is coupled to the G protein Gas, which subsequently activates adenylyl cyclase, increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP). Increased cAMP in neurons is typically excitatory and can induce an action potential by modulating the activity of ion channels.
D1 (DRD1)
D2-like family (inhibitory)
D2-like activation is coupled to the G protein Gai, which subsequently increases phosphodiesterase activity. Phosphodiesterases break down cAMP, producing an inhibitory effect in neurons.
1. The D2Sh are pre-synaptic situated, having modulatory functions (called autoreceptor, they regulate the neurotransmission by feed-back mechanisms, i.e., synthesis, storage and release of dopamine into the synaptic cleft).
2. The D2Lh may have the classic function of a post-synaptic receptor, i.e., keep going on the neurotransmission (excitatory or inhibitory) once blocked by a receptor antagonist or stimulated by the endogenous neurotransmitter itself or a synthetic full or partial agonist.
Molecular Biology of the Dopamine Receptor Subtypes
Dopamine Receptor Expression in the Central Nervous System
