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D 5 receptor is a subtype of the dopamine receptor that has a 10-fold higher affinity for dopamine than the D 1 subtype. [6] The D 5 subtype is a G-protein coupled receptor, which promotes synthesis of cAMP by adenylyl cyclase via activation of Gα s/olf family of G proteins. [7] [8] Both D 5 and D 1 subtypes activate adenylyl cyclase.
D 1 receptor has a high degree of structural homology to another dopamine receptor, D 5, and they both bind similar drugs. [13] As a result, none of the known orthosteric ligands is selective for the D 1 vs. the D 5 receptor, but the benzazepines generally are more selective for the D 1 and D 5 receptors versus the D 2-like family. [12]
The D 1-like receptors are a subfamily of dopamine receptors that bind the endogenous neurotransmitter dopamine. [1] The D 1 -like subfamily consists of two G protein–coupled receptors that are coupled to G s and mediate excitatory neurotransmission , of which include D 1 and D 5 . [ 2 ]
Dopamine receptors are implicated in many neurological processes, including motivational and incentive salience, cognition, memory, learning, and fine motor control, as well as modulation of neuroendocrine signaling. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders. [2]
Dopamine receptor flow chart. Dopamine receptors are all G protein–coupled receptors, and are divided into two classes based on which G-protein they are coupled to. [1] The D 1-like class of dopamine receptors is coupled to Gα s/olf and stimulates adenylate cyclase production, whereas the D 2-like class is coupled to Gα i/o and thus inhibits adenylate cyclase production.
Cell types: Neurons in the nucleus accumbens are mostly medium spiny neurons (MSNs) containing mainly D1-type (i.e., DRD1 and DRD5) or D2-type (i.e., DRD2, DRD3, and DRD4) dopamine receptors. A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA.
Medium spiny neurons have two primary phenotypes (characteristic types): D1-type MSNs of the direct pathway and D2-type MSNs of the indirect pathway. [2] [3] [4] Most striatal MSNs contain only D1-type or D2-type dopamine receptors, but a subpopulation of MSNs exhibit both phenotypes. [2] [3] [4]
Such heteromers may be between receptors from the same family (e.g., adenosine A 1 /A 2A heteromers [9] [10] and dopamine D 1 /D 2 [11] and D 1 /D 3 heteromers [12]) or between entirely unrelated receptors such as CB 1 /A 2A, [13] glutamate mGluR 5 / adenosine A 2A heteromers, [14] cannabinoid CB 1 / dopamine D 2 heteromers, [15] and even CB 1 ...