Autoreceptor

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File:Autorezeptor.png
A pre-synaptic neuron (left) releases a neurotransmitter, here nor-adrenaline (norepinephrine), into the synaptic cleft. There the transmitter acts on the receptors of the post-synaptic neuron (right), but also on autoreceptors of the pre-synaptic neuron. Activation of these autoreceptors typically inhibits further release of the neurotransmitter.

An autoreceptor is a receptor located on presynaptic nerve cell membranes and serves as a part of a feedback loop in signal transduction. It is sensitive only to those neurotransmitters or hormones that are released by the neuron in whose membrane the autoreceptor sits.

Canonically, a presynaptic neuron releases the neurotransmitter across a synaptic cleft to be detected by the receptors on a postsynaptic neuron. Autoreceptors on the presynaptic neuron will also detect this neurotransmitter and often function to control internal cell processes, typically inhibiting further release or synthesis of the neurotransmitter. Thus, release of neurotransmitter is regulated by negative feedback. Autoreceptors are usually G protein-coupled receptors (rather than transmitter-gated ion channels) and act via a second messenger.[1]

Autoreceptors may be located anywhere on the cell body: near the terminal at the axon, on the soma, or on the dendrites.[2]

As an example, norepinephrine released from sympathetic neurons may interact with alpha-2A and alpha-2C receptors to inhibit neurally released norepinephrine. Similarly, acetylcholine released from parasympathetic neurons may interact with muscarinic-2 and muscarinic-4 receptors to inhibit neurally released acetylcholine. An atypical example is given by the β-adrenergic autoreceptor in the sympathetic peripheral nervous system, which acts to increase transmitter release.[2]

Autoreceptors function with TAAR1, a recently discovered GPCR, to regulate monoaminergic systems in the brain. Active TAAR1 opposes the autoreceptor by inactivating the dopamine transporter (DAT).[3][4] In their review of TAAR1 in monoaminergic systems, Xie and Miller proposed this schematic: synaptic dopamine binds to the dopamine autoreceptor, which activates the DAT. Dopamine enters the presynaptic cells and binds to TAAR1, which increases adenylyl cyclase activity. This eventually allows for the translation of trace amines in the cytoplasm and activation of cyclic nucleotide-gated ion channels, which further activate TAAR1 and dump dopamine into the synapse. Through a series of phosphorylation events related to PKA and PKC, active TAAR1 inactivates DAT, preventing uptake of dopamine from the synapse.[5] The presence of two presynaptic receptors with opposite abilities to regulate monoamine transporter function allows for regulation of the monoaminergic system.

An example of an autoreceptor's functioning occurs in the depression of PPF (post-synaptic potential facilitation). A feedback cell is activated by the (partially) depolarized post-synaptic neuron. The feedback cell releases a neurotransmitter to which the autoreceptor of the presynaptic neuron is receptive. The autoreceptor causes the inhibition of calcium channels (slowing calcium ion influx) and the opening of potassium channels (increasing potassium ion efflux) in the presynaptic membrane. These changes in ion concentration effectively diminish the amount of the original neurotransmitter released by the presynaptic terminal into the synaptic cleft. This causes a final depression on the activity of the postsynaptic neuron. Thus the feedback cycle is complete.

See also

References

  1. Template:Cite book
  2. 2.0 2.1 Template:Cite book
  3. PMID 17234900 (PubMed)
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  4. PMID 18310473 (PubMed)
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  5. PMID 19482011 (PubMed)
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