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.
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.


CONCLUSIONS
alpha9/alpha10nAChR is a target for modulation by endomorphin-1 and dynorphin B, efferent cotransmitters in the inner ear.
Lioudyno
M I
MI
Department of Pharmacology, Tulane University, New Orleans, Louisiana 70112, USA. lioudyno@bme.jhu.edu
Verbitsky
M
M
Glowatzki
E
E
Holt
J C
JC
Boulter
J
J
Zadina
J E
JE
Elgoyhen
A B
AB
Guth
P S
PS
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001001:Anura; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D004399:Dynorphins / Q000494:pharmacology / Q000502:physiology*; D007758:Ear, Inner / Q000502:physiology*; D004553:Electric Conductivity; D004723:Endorphins / Q000494:pharmacology / Q000502:physiology*; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D012444:Saccule and Utricle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D014982:Xenopus laevis
D004723:Endorphins; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D020033:Protein Isoforms; D011978:Receptors, Nicotinic; C105293:endomorphin 1; D004399:Dynorphins; C036200:rimorphin; D020881:Enkephalin, D-Penicillamine (2,5)-; D000109:Acetylcholine