Autoreceptor

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.

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

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.

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.