Effects of the plant alkaloid tetrandrine on human nicotinic acetylcholine receptors

Abstract

Functional effects of the well-characterized antagonist of L-type Ca2 + channels tetrandrine on recombinant human g-aminobutyric acid type A (GABAA) (a1h2g2s) receptor or human a7, a4h2, a1h1yg and a1h1yq 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 a4h2>a7>a1h1ygia1h1yq. Functional inhibition of a4h2 and a1h1yg receptors was noncompetitive, but only inhibition of a1h1yg receptors was voltage-dependent. Binding of 125I-a-bungarotoxin to a1h1yg or 3H-cytisine to a4h2 receptors was also inhibited by tetrandrine, but inhibition was noncompetitive and required concentrations higher than those needed to inhibit receptor function. Inhibition of both a7 receptor function and binding of 125I-a-bungarotoxin to a7 receptor were mixed competitive/noncompetitive and occurred at a similar concentration range.