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Neurotransmitter G Protein-Coupled Receptors

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Neurotransmitter G Protein-Coupled Receptors

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Neurotransmitter G Protein-Coupled Receptors Background

The activity of neurons is controlled by groups of neurotransmitter receptors rather than by individual receptors. Neurotransmitter receptors are membrane receptor proteins which exist in neuronal and glialcells. They exist in both postsynaptic neurons and presynaptic neurons. The former being used to receive neurotransmitters and the latter can prevent further release of a given neurotransmitter. Neurotransmitter receptors can bind to neurotransmitters and thus change membrane potential of a neuron. Neurotransmitter receptors are able to receive signals that trigger an electrical signal by regulating the activity of ion channels.

Neurotransmitter receptors are membrane receptor proteins which exist in neuronal and glialcells. They exist in both postsynaptic neurons and presynaptic neurons. The former being used to receive neurotransmitters and the latter can prevent further release of a given neurotransmitter. Neurotransmitter receptors can bind to neurotransmitters and thus change membrane potential of a neuron. Neurotransmitter receptors are able to receive signals that trigger an electrical signal by regulating the activity of ion channels. Neurotransmitters (Figure1) are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another "target" neuron, muscle cell, or gland cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are readily available from the diet and only require a small number of biosynthetic steps for conversion. Neurotransmitters play a major role in shaping everyday life and functions.

Structure of a typical chemical synapse.Figure 1. Structure of a typical chemical synapse.

Classifications

Neurotransmitter receptors can be divided into two types: ligand-gated receptors or ionotropic receptors and G protein-coupled receptors or metabotropic receptors. Ligand-gated receptors can be excited by neurotransmitters like glutamate and aspartate. They are inhibited by neurotransmitters like GABA and glycine. While G protein-coupled receptors are neither excitatory nor inhibitory, taken up a large part of neurotransmitter receptors, they modulate the actions of excititory and inhibitory neurotransmitters. This is a single pore which is composed by five individual protein subunits in ligand-gated receptors. When a neurotransmitter reaches the extracellular recognition site, ions can pass through the pore. This results in the change of a neuron's membrane potential. This usually occurs a millisecond or two after the action potential has been received and lasts only up to ten milliseconds. G protein-coupled receptors function differently. When a neurotransmitter associates with the extracellular recognition site, a G-protein, is activated and opens or closes ion channels located at other places on the cell membrane. G protein-coupled receptors' action is slower. Depolarization takes longer, typically lasting up to hundreds of milliseconds, and in some cases, going on for several minutes, hours, or even days.

Localization

Neurotransmitter (NT) receptors are located on the surface of neuronal (Figure 2) and glial cells. At a synapse, one neuron sends messages to the other neuron via neurotransmitters. Therefore, the postsynaptic neuron, the one receiving the message, clusters NT receptors at this specific place in its membrane. NT receptors can be inserted into any region of the neuron's membrane such as dendrites, axons, and the cell body. Receptors can be located in different parts of the body to act as either an inhibitor or an excitatory receptor for a specific Neurotransmitter. An example of this are the receptors for the neurotransmitter Acetylcholine (ACh), one of the receptors is located at the neuromuscular junction in skeletal muscle to facilitate muscle contraction (excitation), while the other receptor is located in the heart to slow down heart rate (inhibitory).

Anatomy of a multipolar neuron.Figure 2. Anatomy of a multipolar neuron.

Desensitization and neurotransmitter concentration

Neurotransmitter receptors are subject to ligand-induced desensitization: That is, they can become unresponsive upon prolonged exposure to their neurotransmitter. Neurotransmitter receptors are present on both postsynaptic neurons and presynaptic neurons with the former being used to receive neurotransmitters and the latter for the purpose of preventing further release of a given neurotransmitter. In addition to being found in neuron cells, neurotransmitter receptors are also found in various immune and muscle tissues. Many neurotransmitter receptors are categorized as a serpentine receptor or G protein-coupled receptor because they span the cell membrane not once, but seven times. Neurotransmitter receptors are known to become unresponsive to the type of neurotransmitter they receive when exposed for extended periods of time. This phenomenon is known as ligand-induced desensitization or downregulation.

References:

1. Overington JP; et al. How many drug targets are there? Nature Reviews Drug Discovery. 2006.5(12):993-6.

2. Filmore; et al. It's a GPCR world. Modern Drug Discovery. 2004.11:24-28.

3. King N; et al. Evolution of key cell signaling and adhesion protein families predates animal origins. Science. 2003,301(5631):361-362.

4. Wettschureck N.; Offermanns S. Mammalian G proteins and their cell type specific functions. Physiological Reviews. 2005,85(4):1159–1204.

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