Arachidonic acid induces a long-lasting facilitation of hippocampal synaptic transmission by modulating PKC activity and nicotinic ACh receptors.

The present study was conducted to understand the effect of arachidonic acid on nicotinic acetylcholine (ACh) receptor-mediated synaptic plasticity. Arachidonic acid persistently (>/=1 h) potentiated currents through neuronal nicotinic ACh receptors (alpha7 and alpha4beta2) expressed in Xenopus oocytes, and the effect was blocked by the selective protein kinase C (PKC) inhibitors, such as GF109203X, PKCI, and co-expressed active PKC inhibitor peptide. This free fatty acid markedly increased nicotine-sensitive glutamate release from hippocampal slices and enhanced the rate of nicotine-sensitive miniature excitatory postsynaptic currents without affecting the amplitude in cultured hippocampal CA1 neurons under the influence of PKC. Furthermore, arachidonic acid induced a long-lasting (>/=3 h) facilitation of hippocampal CA1 synaptic transmission in slices, and the effect was blocked by nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. The facilitation, whereas independent of N-methyl-D-aspartate (NMDA) receptors, shares a common mechanism with long-term potentiation (LTP) induced by tetanic stimulation. The results of the present study thus suggest that arachidonic acid sustains enhanced activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to an 'LTP-like' facilitation of hippocampal synaptic transmission.

[1]  R. Gray,et al.  Hippocampal synaptic transmission enhanced by low concentrations of nicotine , 1996, Nature.

[2]  G. Enikolopov,et al.  Amplification of calcium-induced gene transcription by nitric oxide in neuronal cells , 1993, Nature.

[3]  Y. Nishizuka.  Protein kinase C and lipid signaling for sustained cellular responses , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  Modulation of ACh receptor currents by arachidonic acid , 1998 .

[5]  J. Sweatt,et al.  Autonomously active protein kinase C in the maintenance phase of N-methyl-D-aspartate receptor-independent long term potentiation. , 1994, The Journal of biological chemistry.

[6]  T. Nishizaki,et al.  Arachidonic acid potentiates ACh receptor currents by protein kinase C activation but not by receptor phosphorylation. , 1996 .

[7]  Alcino J. Silva,et al.  Modified hippocampal long-term potentiation in PKCγ-mutant mice , 1993, Cell.

[8]  Thomas C. Südhof,et al.  The synaptic vesicle cycle: a cascade of protein–protein interactions , 1995, Nature.

[9]  M. Segal,et al.  Muscarinic receptors involved in hippocampal plasticity. , 1997, Life sciences.

[10]  Robert C. Malenka,et al.  Potentiation of synaptic transmission in the hippocampus by phorbol esters , 1986, Nature.

[11]  B. Platt,et al.  GABA-induced long-term potentiation in the guinea-pig superior colliculus , 1998, Neuropharmacology.

[12]  P. Clarke,et al.  Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  S. Wonnacott.  Neuronal nicotinic receptors: functional correlates of ligand binding sites. , 1991, Biochemical Society transactions.

[14]  S. Wonnacott,et al.  Presynaptic nicotinic ACh receptors , 1997, Trends in Neurosciences.

[15]  T. Nishizaki,et al.  Direct action of 4-β-phorbol-12,13-dibutyrate (PDBu) on nicotinic acetylcholine receptor channel independent of protein kinase C activation , 1995, Neuroscience Letters.

[16]  R. Nicoll,et al.  Mechanisms underlying long-term potentiation of synaptic transmission. , 1991, Annual review of neuroscience.

[17]  E X Albuquerque,et al.  Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function. , 1997, The Journal of pharmacology and experimental therapeutics.

[18]  T. Nishizaki,et al.  Activation of endogenous protein kinase C enhances currents through α1 and α2 glycine receptor channels , 1995, Brain Research.

[19]  Roberto Malinow,et al.  Persistent protein kinase activity underlying long-term potentiation , 1988, Nature.

[20]  S. Rogers,et al.  A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. , 1992, Molecular pharmacology.

[21]  G. Collingridge,et al.  Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus , 1991, Nature.

[22]  J P Changeux,et al.  Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal alpha 7 nicotinic receptor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[23]  C. Tanaka,et al.  Cellular and intracellular localization of ε-subspecies of protein kinase C in the rat brain; presynaptic localization of the ε-subspecies , 1993, Brain Research.

[24]  L. Role,et al.  Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. , 1995, Science.

[25]  P. Whiting,et al.  Hippocampal nicotinic autoreceptors modulate acetylcholine release. , 1993, Biochemical Society transactions.

[26]  E. Albuquerque,et al.  Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes. , 1993, The Journal of pharmacology and experimental therapeutics.

[27]  J. Lindstrom,et al.  Immunocytochemical localization of the α7 subunit of the nicotinic acetylcholine receptor in the rat central nervous system , 1994, The Journal of comparative neurology.

[28]  C. Tanaka,et al.  Electron microscopic localization of γ- and βII-subspecies of protein kinase C in rat hippocampus , 1990, Brain Research.

[29]  P. Andersen,et al.  Protein kinase C injection into hippocampal pyramidal cells elicits features of long term potentiation , 1987, Nature.

[30]  Y. Ben-Ari,et al.  Novel form of long-term potentiation produced by a K+channel blocker in the hippocampus , 1991, Nature.

[31]  T. Nishizaki,et al.  Arachidonic acid as a messenger for the expression of long-term potentiation. , 1999, Biochemical and biophysical research communications.

[32]  J Patrick,et al.  Distribution of alpha2, alpha3, alpha4, and beta2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: A hybridization histochemical study in the rat , 1989, The Journal of comparative neurology.

[33]  Y. Nishizuka,et al.  The protein kinase C family for neuronal signaling. , 1994, Annual review of neuroscience.

[34]  H. Koide,et al.  Characterization of protein kinase C in Xenopus oocytes. , 1992, Biochemical and biophysical research communications.