Presynaptic neuropeptide receptors

Presynaptic receptors for four families of neuropeptides will be discussed: opioids, neuropeptide Y, adrenocorticotropic hormone (ACTH), and orexins. Presynaptic receptors for the opioids (micro, delta, kappa, and ORL(1)) and neuropeptide Y (Y(2)) inhibit transmitter release from a variety of neurones, both in the peripheral and central nervous systems. These receptors, which were also identified in human tissue, are coupled to G(i/o) proteins and block voltage-dependent Ca(2+) channels, activate voltage-dependent K(+) channels, and/or interfere with the vesicle release machinery. Presynaptic receptors for ACTH (MC(2) receptors) have so far been identified almost exclusively in cardiovascular tissues from rabbits, where they facilitate noradrenaline release; they are coupled to G(s) protein and act via stimulation of adenylyl cyclase. Presynaptic receptors for orexins (most probably OX(2) receptors) have so far almost exclusively been identified in the rat and mouse brain, where they facilitate the release of glutamate and gamma-aminobutyric acid (GABA); they are most probably linked to G(q) and directly activate the vesicle release machinery or act via a transduction mechanism upstream of the release process. Agonists and antagonists 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.