Effects Of The Plant Alkaloid Tetrandrine On Human Nicotinic Acetylcholine Receptors
Functional effects of the well-characterized antagonist of L-type Ca2+ channels tetrandrine on recombinant human Î³-aminobutyric acid type A (GABAA) (Î±1Î²2Î³2s) receptor or human Î±7, Î±4Î²2, Î±1Î²1Î´Î³ and Î±1Î²1Î´Îµ nicotinic acetylcholine receptors expressed in Xenopus oocytes were examined using two-electrode voltage clamp. Tetrandrine inhibited the function of acetylcholine nicotinic receptors, but it had no effect on GABAA receptors. Potency of inhibition was influenced by the receptor subtype and the rank order was Î±4Î²2>Î±7>Î±1Î²1Î´Î³â‰…Î± 1Î²1Î´Îµ. Functional inhibition of Î±4Î²2 and Î±1Î²1Î´Î³ receptors was noncompetitive, but only inhibition of Î±1Î²1Î´Î³ receptors was voltage-dependent. Binding of 125I-Î±-bungarotoxin to Î±1Î²1Î´Î³ or 3H-cytisine to Î±4Î²2 receptors was also inhibited by tetrandrine, but inhibition was noncompetitive and required concentrations higher than those needed to inhibit receptor function. Inhibition of both Î±7 receptor function and binding of 125I-Î±-bungarotoxin to Î±7 receptor were mixed competitive/noncompetitive and occurred at a similar concentration range. Â© 2002 Elsevier Science B.V. All rights reserved.
European Journal of Pharmacology
Digital Object Identifier (DOI)
Slater, Yvonne; Houlihan, Lee M.; Cassels, Bruce K.; Lukas, Ronald J.; and Bermudez, Isabel, "Effects Of The Plant Alkaloid Tetrandrine On Human Nicotinic Acetylcholine Receptors" (2002). Translational Neuroscience. 217.