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 α7 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 μM) inhibits acetylcholine (ACh)-induced α7 receptor-mediated currents. The effect of bisabolol was not dependent on the membrane potential. Bisabolol inhibition was not changed by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free solution containing Ba(2+), suggesting that endogenous Ca(2+)-dependent Cl(-) channels are not involved in bisabolol actions. Increasing the concentrations of ACh did not reverse bisabolol inhibition. Furthermore, the specific binding of [(125)I] α-bungarotoxin was not attenuated by bisabolol. Choline-induced currents in CA1 interneurons of rat hippocampal slices were also inhibited with IC50 of 4.6 μM. Collectively, our results suggest that bisabolol directly inhibits α7-nAChRs via a binding site on the receptor channel.
Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
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Nurulain
Department of Biological Sciences, Schmid College of Science and Technology, Chapman University, One University Drive, Orange, CA 92866, USA.
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Prytkova
Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
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Sultan
Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
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Ievglevskyi
Department of Cellular Biology & Pharmacology, College of Medicine, Florida International University, Miami, FL 33199, USA.
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Lorke
Laboratory of Functional Lipidomics, Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
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Yang
Department of Cellular Biology & Pharmacology, College of Medicine, Florida International University, Miami, FL 33199, USA.
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Petroianu
Laboratory of Functional Lipidomics, Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
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Howarth
Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, 4400 University Drive, Fairfax, VA 22030, USA.
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Kabbani
Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates. Electronic address: Murat_Oz@uaeu.ac.ae.
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Oz
D000818:Animals; D002038:Bungarotoxins / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D008958:Models, Molecular; D000081222:Monocyclic Sesquiterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000502:physiology*
D002038:Bungarotoxins; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; D064569:alpha7 Nicotinic Acetylcholine Receptor; C004497:bisabolol; D002118:Calcium
Xenopus oocyte; bisabolol; hippocampus neurons; nicotine; nicotinic acetylcholine receptor