Chemical messengers in the body exert their effects by binding to receptors, much like a key fits in a lock to open a door. The nerve messenger dopamine mediates multiple important effects in the brain, and its activity is tightly regulated through a complex system of receptors with different functions located at various sites throughout the brain.
Definition
Dopamine is a neurotransmitter, a chemical released by nerves to communicate with other nerves or with muscles. Dopamine is released into space between nerves called a synapse. It diffuses across the space and binds to specific molecules called dopamine receptors in the membranes of the cells on the other side of the synapse. Receptor binding sets off electrical changes in the cell. Dopamine and its receptors are found in parts of the brain concerned with movement, reward-seeking, and learning and memory.
Mechanism
Unlike the majority of neurotransmitter receptors, dopamine receptors are metabotropic receptors, meaning that instead of directly opening membrane channels to start an electrical current, they work through a series of relays of small molecules, called a second messenger system, to effect their changes. Although this mechanism is slower, it allows for finer control of the response.
Types
Scientists have identified five different dopamine receptors, named D1 through D5. They occur in different populations of cells and have different capacity to bind dopamine tightly. D1 and D5 receptors are structurally similar to each other, and D2, D3 and D4 receptors form another structural family. The two families tend to have opposite cellular effects. In addition, mixed pairs of receptors like a D1-D2 pair or a D5-D2 pair can interact to finely tune cellular responses to dopamine.
Disease
When dopamine binds the D2 receptor, it activates the extrapyramidal system of the brain, the functional network of the brain that controls posture and the start and stop of movements. People with Parkinson's disease develop tremors and other symptoms because they lack adequate levels of dopamine to normally stimulate the D2 receptors. Patients suffering from schizophrenia have problems with their dopamine system, especially the actions of D3 and D4 receptors that are heavily involved in processing thoughts. Drug addiction powerfully stimulates dopamine release, to the point where the body scales back the production and activity of dopamine receptors to try to compensate. Over time, the lack of receptor activity makes the brain less able to respond to normal levels of dopamine.
Medications
The drug levodopa is a precursor to dopamine. Once in the body, enzymes convert levodopa to dopamine and it binds to dopamine receptors, making it a valuable drug for treating Parkinson's disease. Drugs chemically similar to dopamine, the dopamine agonists ropinirole and pramipexole, bind to dopamine D2 receptors, and possibly other subtypes, to quiet the symptoms of Parkinson's. Drugs that block D3 and D4 receptors can help control the symptoms of schizophrenia.
References
- Merck Manual: Neurotransmission
- Merck Manual: Parkinson's Disease
- National Institute of Drug Abuse: Science of Addiction
- "Current Opinion in Pharmacology"; Ahmed Hasbi, Brian O'Dowd and Susan George; Heteromerization of dopamine D2 receptors with dopamine D1 or D5 generates intracellular calcium signaling by different mechanisms; February, 2010.
