Effects of apigenin on the function of human α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes

The effects of apigenin, a plant flavonoid, were investigated using the two-electrode voltage-clamp technique on the function of the cloned alpha 7 subunit of the human nicotinic acetylcholine (alpha 7-nACh) receptor expressed in Xenopus oocytes. Currents induced by ACh (100 mu M) were reversibly potentiated by apigenin with an EC50 value of 5.4 mu M in a voltage-independent manner. In addition, potentiation by apigenin was significantly diminished by increasing ACh concentrations. Furthermore, apigenin (30 mu M) did not alter the specific binding of [125I] alpha-bungarotoxin in oocyte membranes. Moreover, 30 mu M apigenin also potentiated [3H] norepinephrine release evoked by nicotine (30 mu M) in rat hippocampal slices. Finally, our docking studies carried out for apigenin on nicotinic alpha 7-nACh receptors suggest that apigenin binds to the transmembrane region of the receptor as an allosteric modulator. Taken together, our results indicate that apigenin allosterically potentiates the function of the human alpha 7-nACh receptors expressed in Xenopus oocytes and hippocampal slices.