Morphine inhibits an alpha9-acetylcholine nicotinic receptor-mediated response by a mechanism which does not involve opioid receptors.
Nicotinic acetylcholine (nACh) receptors are known to be targets for modulation by a number of substances, including the opiates. It is known that acetylcholine (ACh) coexists with opioid peptides in cochlear efferent neurons, and such a colocalization has been proposed for the vestibular system. In the present study we test the hypothesis that morphine, an opioid receptor agonist with a broad spectrum of selectivity, modulates alpha9nACh receptor-mediated responses in frog vestibular hair cells. Morphine dose-dependently and reversibly inhibited ACh-induced currents as recorded by the perforated patch-clamp method. In the presence of morphine the ACh dose-response curve was shifted to the right in a parallel fashion, suggesting a competitive interaction. However, naloxone did not antagonize the inhibition produced by morphine. To test the hypothesis that morphine could interact with the alpha9nACh receptor without the involvement of opioid receptors, experiments were performed using Xenopus laevis oocytes injected with the alpha9nACh receptor cRNA. The currents activated by ACh in Xenopus oocytes, a system that lacks opioid receptors, were also dose-dependently inhibited by morphine. We conclude that morphine inhibits the alpha9nACh receptor-mediated response in hair cells and Xenopus oocytes through a mechanism which does not involve opioid receptors but may be a direct block of the alpha9nACh receptor.
Lioudyno
M I
MI
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA. mlioudy@mailhost.tcs.tulane.edu
Verbitsky
M
M
Holt
J C
JC
Elgoyhen
A B
AB
Guth
P S
PS
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004553:Electric Conductivity; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D011894:Rana pipiens; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology*; D014982:Xenopus laevis
C402445:Chrna9 protein, mouse; D009292:Narcotic Antagonists; D009294:Narcotics; D011978:Receptors, Nicotinic; D009270:Naloxone; D009020:Morphine; D000109:Acetylcholine