heteroreceptors

Heteroreceptors are receptors located on a neuron that respond to neurotransmitters released by other, neighboring neurons. They are contrasted with autoreceptors, which respond to the neuron’s own transmitter. Heteroreceptors are often presynaptic and modulate the release of neurotransmitters from the neuron on which they reside, helping to regulate synaptic strength and information flow within neural circuits.

Most heteroreceptors are G protein–coupled receptors. Activation of these receptors can either inhibit or facilitate transmitter release, typically by altering presynaptic calcium influx, modulating potassium channels, or changing intracellular second messenger systems such as cAMP or IP3/DAG. A prominent example is the endocannabinoid system, where presynaptic CB1 receptors on various terminals respond to endocannabinoids released from postsynaptic neurons to suppress neurotransmitter release. Other examples include presynaptic GABA_B receptors on glutamatergic terminals and certain serotonin receptors (such as 5-HT1B/1D) on terminals of other neurons, which can modulate the release of their targets.

Physiological significance and pharmacology: Heteroreceptors contribute to the fine-tuning of synaptic transmission, shaping temporal dynamics, plasticity, and network excitability. They are important for coordinating activity across neural circuits and can influence learning, mood, pain perception, and motor control. Many drugs act, at least in part, by targeting heteroreceptors to modulate presynaptic neurotransmitter release, providing therapeutic avenues for conditions such as epilepsy, mood disorders, and pain.