Search

Presynaptic receptors for four families of neuropeptides will be discussed: opioids, neuropeptide Y, adrenocorticotropic hormone (ACTH), and orexins. Presy- naptic receptors for the opioids (µ, δ, κ, and ORL1) and neuropeptide Y (Y2) inhibit transmitter release from a variety of neurones, both in the peripheral and cen- tral nervous systems. These receptors, which were also identified in human tissue, are coupled to Gi/o proteins and block voltage-dependent Ca 2+ channels, activate voltage-dependent K + channels, and/or interfere with the vesicle release machin- ery. Presynaptic receptors for ACTH (MC2 receptors) have so far been identified almost exclusively in cardiovascular tissues from rabbits, where they facilitate nora- drenaline release; they are coupled to Gs protein and act via stimulation of adenylyl cyclase. Presynaptic receptors for orexins (most probably OX2 receptors) have so far almost exclusively been identified in the rat and mouse brain, where they fa- cilitate the release of glutamate and γ-aminobutyric acid (GABA); they are most probably linked to Gq and directly activate the vesicle release machinery or act via a transduction mechanism upstream of the release process. Agonists and an- tagonists at opioid receptors owe at least part of their therapeutic effects to actions on presynaptic receptors. Therapeutic drugs targeting neuropeptide Y and orexin receptors and presynaptic ACTH receptors so far are not available.

The amount of serotonin (5-hydroxytryptamine; 5-HT) released from the varicosities of the serotoninergic axon terminals in response to invading action potentials at a given frequency is by no means constant. As generally accepted now, exocytotic release of 5-HT can be significantly modified by presynaptic receptors, i.e. receptors located on the serotoninergic axon terminals (for reviews, see Moret 1985; Middlemiss 1988; Starke et al. 1989; Gothert 1990). When such receptors are stimulated by 5-HT released from the serotoninergic axon terminals, they are termed presynaptic 5-HT autoreceptors. When receptors on the serotoninergic axon terminals are activated by other transmitters released from non-serotoninergic neurons, they are denoted as presynaptic heteroreceptors. In the latter case, the axon terminals of these neurons may form axo-axonic synapses with the serotoninergic terminals, or the interacting neighbouring neurons may release their transmitter non-synaptically into the extracellular space and, thus, may influence larger neuronal territories including the serotoninergic axon terminals (Beaudet and Descarries 1978; Tork 1990).