Inhibition of the neuronal nicotinic receptor-mediated current by kappa opioid receptor agonists in PC12 cells.
The authors studied effects of opioid receptor agonists on neuronal nicotinic-receptor-mediated current in PC12 cells using whole-cell current recording. At 1 microM, [d-Ala, N-Me, Phe, Gly-ol]- enkephalin (DAMGO), a selective micro receptor agonist, or 10 microM methionine-enkephalin, a micro and delta receptor agonist, did not inhibit the current elicited by 30 microM nicotine significantly. Dynorphin A (1-17) (0.1-1 microM), an endogenous kappa receptor agonist, and U50488 (0.1-10 microM), a non-peptide selective kappa receptor agonist, depressed the nicotine-induced current reversibly in a dose-dependent manner. They accelerated the current decay, resulting in greater effects on the non-desensitized current than the peak current. These effects were not affected by nor-binaltrophimine, a selective kappa receptor antagonist, or by inclusion of guanosine 5'-O-(2-thiobiphosphate) (GDP[beta-S]), a GTP binding protein blocker, into the pipette solution. These results demonstrate that two kappa opioid receptor agonists, dynorphin A (1-17) and U50488, inhibit neuronal nicotinic-receptor-mediated current without the involvement of opioid receptors or GTP binding proteins. The acceleration of the current decay suggests a direct action on nicotinic receptors such as open channel block, or augmentation of desensitization. Modulation of neuronal nicotinic receptors by dynorphins may play a role in some areas where dynorphin release sites and neuronal nicotinic receptors are colocalized.
Oka
K
K
Department of Anesthesiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan.
Andoh
T
T
Watanabe
I
I
Kamiya
Y
Y
Ito
H
H
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D004553:Electric Conductivity; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D004745:Enkephalins; D009292:Narcotic Antagonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C051844:norbinaltorphimine; D004744:Enkephalin, Methionine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins