The alpha9/alpha10-containing nicotinic ACh receptor is directly modulated by opioid peptides, endomorphin-1, and dynorphin B, proposed efferent cotransmitters in the inner ear.

TitleThe alpha9/alpha10-containing nicotinic ACh receptor is directly modulated by opioid peptides, endomorphin-1, and dynorphin B, proposed efferent cotransmitters in the inner ear.
Publication TypeJournal Article
Year of Publication2002
AuthorsLioudyno, MI, Verbitsky M, Glowatzki E, Holt JC, Boulter J, Zadina JE, Elgoyhen AB, Guth PS
JournalMolecular and cellular neurosciences
Volume20
Issue4
Pagination695-711
Date Published2002 Aug
ISSN1044-7431
Keywordsacetylcholine, Animals, Anura, Cochlea, Dynorphins, Ear, Inner, Electric Conductivity, Endorphins, Enkephalin, D-Penicillamine (2,5)-, Hair Cells, Auditory, Neurotransmitter Agents, Oligopeptides, Oocytes, Protein Isoforms, Rats, Rats, Sprague-Dawley, Receptors, Nicotinic, Receptors, Opioid, Saccule and Utricle, Synapses, Xenopus laevis
Abstract

Opioid peptides have been detected in the auditory and vestibular efferent neurons where they colocalize with the major neurotransmitter, acetylcholine. We investigated the function of opioids to modulate neurotransmission mediated by hair cell's alpha9/alpha10-containing nicotinic acetylcholine receptors (alpha9/alpha10nAChRs). The endogenous opioid peptides, endomorphin-1 (mu agonist) and dynorphin B (kappa agonist), but not a delta agonist [D-Pen2,D-Pen-5]enkephalin, inhibited the acetylcholine-evoked currents in frog saccular hair cells and rat inner hair cells. This inhibition was noncompetitive, voltage-independent, and was accompanied by an acceleration of the rate of current decay. Selective mu- and kappa-opioid receptor antagonists did not block the inhibition, although partial reduction by naloxone was observed. All opioid antagonists tested also reduced the acetylcholine response. Endomorphin-1 and dynorphin B inhibited the acetylcholine-evoked currents in alpha9/alpha10-expressing Xenopus oocytes. Because oocytes lack opioid receptors, it provides strong evidence for the direct interaction of opioid peptides with alpha9/alpha10nAChR. CONCLUSION: alpha9/alpha10nAChR is a target for modulation by endomorphin-1 and dynorphin B, efferent cotransmitters in the inner ear.

Alternate JournalMol. Cell. Neurosci.