Presynaptic Neuropeptide Receptors

Abstract

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.

Orexin A modulates neuronal activity of the rodent suprachiasmatic nucleus in vitro

“…These experiments indicated that the frequency of sIPSCs is altered by orexin A. This change in sIPSC frequency could be due to an alteration of spike‐dependent release of neurotransmitter from presynaptic cells, or, alternatively, could result from a direct effect of orexin A on the vesicle release machinery in presynaptic terminals, as was proposed for other hypothalamic neurons (Schlicker & Kathmann, 2008). Because orexin can increase cytosolic calcium levels in neurons independently of action potentials, it was also suggested that orexin may enhance presynaptic transmitter release by a parallel mechanism of increasing calcium levels of the presynaptic bouton, which would enhance calcium‐dependent transmitter release (van den Pol et al.…”

Excitation of Histaminergic Tuberomamillary Neurons by Thyrotropin-Releasing Hormone

“…Whereas orexin enhances the frequency of sIPSCs recorded from TMN neurons, dynorphin inhibits it; when both peptides are coapplied, the effect of dynorphin dominates (Eriksson et al, 2001a). Presynaptic -opioid receptors inhibit transmitter release from a variety of neurons activating voltage-dependent K ϩ channels (Schlicker and Kathmann, 2008). Our experiments with the -opioid receptor antagonist nor-binaltorphimine indicated that endogenous dynorphin is unlikely responsible for the TRHmediated inhibition of presynaptic GABA release, as such inhibi- …”

Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B

“…In our H295R cells, this occurred significantly for ORA but not ORB, consistent with the primary cell and ex vivo data. It is known that pre-synaptic receptors for orexins in the rat and mouse brain facilitate the release of glutamate and gamma-amino butyric acid; probably directly activating the vesicle release machinery or acting via a transduction mechanism upstream of the release process (Schlicker & Kathmann 2008). Furthermore, ORA and ORB have recently been shown to have different secretion patterns for glutamate release (Borgland et al 2008).…”