8‐[2‐(2‐pentyl‐cyclopropylmethyl)‐cyclopropyl]‐octanoic acid stimulates GABA release from interneurons projecting to CA1 pyramidal neurons in the rat hippocampus via pre‐synaptic α7 acetylcholine receptors

Nicotinic acetylcholine (ACh) receptors, such as α7, α3β4 and α4β2 receptors in the hippocampus, are suggested to modulate neurotransmitter release. 8‐[2‐(2‐Pentyl‐cyclopropylmethyl)‐cyclopropyl]‐octanoic acid (DCP‐LA) (100 nm), a linoleic acid derivative, potentiated responses of α7, α3β4 and α4β2 ACh receptors expressed in Xenopus oocytes that are blocked by 3‐(1‐[dimethylaminopropyl] indol‐3‐yl)‐4‐[indol‐3‐yl] maleimide (GF109203X), a selective inhibitor of protein kinase C (PKC), except for α3β4 ACh receptors. DCP‐LA enhanced the nicotine‐triggered release of GABA from rat hippocampal slices in the presence of tetrodotoxin in a bell‐shaped dose‐dependent manner at concentrations ranging from 10 nm to 10 µm, although DCP‐LA by itself had no effect on GABA release. The DCP‐LA action was inhibited by GF109203X or α‐bungarotoxin, an inhibitor of α7 ACh receptors, but not by mecamylamine or dihydro‐β‐erithroidine, an inhibitor of α3β4 and α4β2 ACh receptors. A similar effect on GABA release was obtained with 12‐O‐tetradecanoylphorbol 13‐acetate, a PKC activator. DCP‐LA (100 nm) also enhanced GABA release triggered by choline, an agonist of α7 ACh receptors, but not 3‐[2(s)‐azetidinylmethoxy] pyridine, an agonist of α4β2 ACh receptors. In addition, DCP‐LA (100 nm) increased the rate of nicotine‐triggered GABAA receptor‐mediated miniature inhibitory post‐synaptic currents, monitored from CA1 pyramidal neurons of rat hippocampal slices, and the effect was also inhibited by GF109203X or α‐bungarotoxin but not by mecamylamine. Thus, the results of the present study indicate that DCP‐LA stimulates GABA release by enhancing activity of pre‐synaptic α7 ACh receptors present on the GABAergic terminals of interneurons that transmit to CA1 pyramidal neurons via a PKC pathway.