Dopamine Synthesis
Dopamine catabolism
- Catabolism of dopamine are monoamine oxidase (MAO) and catechol O-methyltransferase (COMT).
- Both neurons and glia contain mitochondrial MAO and cytoplasmic COMT. Inhibitors of these enzymes, such as phenelzine and tranylcypromine, are used clinically as antidepressants.
- Dopamine action in the synaptic cleft is terminated by re-uptake of dopamine into nerve terminals or surrounding glial cells by a Na+-dependent dopamine transporter, termed DAT.
- Cocaine apparently produces its psychotropic effects by binding to and inhibiting DAT, yielding a net increase in dopamine release from specific brain areas.
- Amphetamine, another addictive drug, also inhibits DAT as well as the transporter for norepinephrine (see below).
Dopamine receptos
D1-like Receptors (D1, D5)
- Coupling & Mechanism: Activate Gs proteins, which stimulate adenylyl cyclase, increasing intracellular cAMP → Excitatory
- Distribution: Highly expressed in the brain, especially in the striatum, cortex, limbic areas, and kidney.
- Behavioral Effects: Mediate many dopamine-induced excitatory effects, such as increased motor activity and reinforcement behaviors.
D2-like Receptors (D2, D3, D4)
- Coupling & Mechanism: Activate Gi/o proteins, which inhibit adenylyl cyclase, causing a decrease in cAMP → inhibitory
- Distribution: Prominent in basal ganglia, limbic system, pituitary gland, and peripheral nervous system.
- Behavioral & Physiological Effects: Associated with inhibition of neurotransmitter release, modulation of movement, emotion, and the endocrine system (e.g., prolactin release inhibition). D2 also acts presynaptically as an autoreceptor, inhibiting further dopamine release.
D3 Receptors
- Coupling & Mechanism: Activate Gi/o proteins, which inhibit adenylyl cyclase, causing a decrease in cAMP → inhibitory
- Role: Regulates emotional responses and cognition, particularly in limbic areas; implicated in psychiatric conditions.
D4 Receptors
- Coupling & Mechanism: Activate Gi/o proteins, which inhibit adenylyl cyclase, causing a decrease in cAMP → inhibitory
- Role: Found in frontal cortex and midbrain regions; related to attention, cognition, and several neuropsychiatric disorders.
D5 Receptors
- Coupling: Activate Gs proteins, which stimulate adenylyl cyclase, increasing intracellular cAMP → Excitatory
- Role: Less common, mainly in hippocampus and hypothalamus; contributes to learning and memory processes.
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