Stearic acid facilitates hippocampal neurotransmission by enhancing nicotinic ACh receptor responses via a PKC pathway.
Of a variety of saturated free fatty acids examined here, those with less than 20 hydrocarbon potentiated responses through Torpedo ACh receptors expressed in Xenopus oocytes, and the maximal effect was obtained with stearic acid (C18:0) at 10 microM (168+/-25% of basal levels 10 min after 10-min treatment). Stearic aid (10 microM) also potentiated alpha7 nicotinic ACh receptor responses, being evident 110 min after 10-min treatment (219+/-18% of basal levels), and the potentiation was inhibited by GF109203X, a selective inhibitor of protein kinase C (PKC). In the PKC assay using a reversed-phase HPLC, stearic acid (10 microM) enhanced PKC-epsilon activity approximately twice as much as the activity in the absence of stearic acid. Stearic acid (10 microM) induced a long-lasting facilitation of neurotransmission in the dentate gyrus of rat hippocampal slices, and the facilitation was inhibited by GF109203X or alpha-bungarotoxin, an inhibitor of alpha7 receptors. The results presented here suggest that stearic acid facilitates hippocampal neurotransmission by enhancing alpha7 receptor responses via a PKC pathway.
Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Kohei
K
Ohta
Hirohito
H
Miyamoto
Takahiro
T
Yaguchi
Kaoru
K
Nagai
Satoshi
S
Yamamoto
Tamotsu
T
Nomura
Akito
A
Tanaka
Tomoyuki
T
Nishizaki
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009865:Oocytes; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013229:Stearic Acids / Q000378:metabolism* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011978:Receptors, Nicotinic; D013229:Stearic Acids; D064569:alpha7 Nicotinic Acetylcholine Receptor; C031183:stearic acid; D011493:Protein Kinase C; C070515:bisindolylmaleimide I