Peptide autoreceptors: does an autoreceptor for substance P exist?

The presence of autoreceptors for simple neurotransmitters at synapses in the mammalian nervous system is well established. By contrast, the evidence for such receptors modifying neuropeptide transmission is less obvious. Probably the most well characterized of the neuropeptides is substance P (SP), which appears to play a major role as a primary afferent modulator. This article highlights evidence to support the existence of autoreceptors that might modulate the release of this neuropeptide and which, therefore, could be important in the design of drugs affecting SP function, not only in sensory processing, but also elsewhere in the brain.