Presynaptic auto- and allelo-receptor regulation of hypothalamic opioid peptide release

Abstract

Recent studies have shown that inhibitory feedback mechanisms regulate the release of the endogenous opioid peptides β-endorphin (acting predominantly at μ opioid receptors in the brain), dynorphin (a κ opioid receptor ligand) and [Met]enkephalin (a δ opioid receptor ligand) from the rat hypothalamus. By using specific antagonists of the various opioid receptor types, it is shown that the release of these peptides from hypothalamic slices in vitro is not only controlled by homologous (auto)-receptors, but that cross-regulation between the three neuronal opioid receptor types also occurs; thus, the δ receptor antagonist N, N-diallyl-Tyr-Aib-Aib-Phe-Leu increases the release of all three peptides, the μ receptor antagonist d-tetrahydroisoquinoline-Cys-Tyr- d-Trp-Arg-Thr-Pen-Thr-NH 2 increases that of β-endorphin and dynorphin, and the κ receptor antagonist nor-binaltorphimine increases that of dynorphin; all these effects occur in the presence of tetrodotoxin, indicating a presynaptic site of action. We propose the term “allelo-receptors” to describe this particular form of neuronal regulation in which an endogenous ligand, acting via its own specific receptor, also regulates the release of related peptides which activate different classes of opioid receptors.