INHIBITORY ACTIONS OF BISABOLOL ON α7-NICOTINIC ACETYLCHOLINE RECEPTORS

Bisabolol is a plant-derived monocyclic sesquiterpene alcohol with antinociceptive and antiinflammatory actions. However, molecular targets mediating these effects of bisabolol are poorly understood. In this study, using a two-electrode voltage-clamp and patch-clamp techniques and live cellular calcium imaging, we have investigated the effect of bisabolol on the function of human alpha 7 subunit of nicotinic acetylcholine receptor (nAChR) in Xenopus oocytes, interneurons of rat hippocampal slices. We have found that bisabolol reversibly and concentration dependently (IC50 = 3.1 mu M) inhibits acetylcholine (ACh)-induced alpha 7 receptor-mediated currents. The effect of bisabolol was not dependent on the membrane potential. Bisabolol inhibition was not changed by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free solution containing Ba2+, suggesting that endogenous Ca2+-dependent Cl- channels are not involved in bisabolol actions. Increasing the concentrations of ACh did not reverse bisabolol inhibition. Furthermore, the specific binding of [I-125] alpha-bungarotoxin was not attenuated by bisabolol. Choline-induced currents in CA1 interneurons of rat hippocampal slices were also inhibited with IC50 of 4.6 mu M. Collectively, our results suggest that bisabolol directly inhibits alpha 7-nAChRs via a binding site on the receptor channel. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.