Effects of the plant alkaloid tetrandrine on human nicotinic acetylcholine receptors.
Functional effects of the well-characterized antagonist of L-type Ca(2+) channels tetrandrine on recombinant human gamma-aminobutyric acid type A (GABA(A)) (alpha1beta2gamma2s) receptor or human alpha7, alpha4beta2, alpha1beta1deltagamma and alpha1beta1delta epsilon 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 GABA(A) receptors. Potency of inhibition was influenced by the receptor subtype and the rank order was alpha4beta2>alpha7>alpha1beta1deltagamma congruent with alpha1beta1delta epsilon. Functional inhibition of alpha4beta2 and alpha1beta1deltagamma receptors was noncompetitive, but only inhibition of alpha1beta1deltagamma receptors was voltage-dependent. Binding of 125I-alpha-bungarotoxin to alpha1beta1deltagamma or 3H-cytisine to alpha4beta2 receptors was also inhibited by tetrandrine, but inhibition was noncompetitive and required concentrations higher than those needed to inhibit receptor function. Inhibition of both alpha7 receptor function and binding of 125I-alpha-bungarotoxin to alpha7 receptor were mixed competitive/noncompetitive and occurred at a similar concentration range.
Slater
Yvonne
Y
Department of Biological and Molecular Sciences, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK.
Houlihan
Lee M
LM
Cassels
Bruce K
BK
Lukas
Ronald J
RJ
Bermúdez
Isabel
I
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C579167:Chrna7 protein, human; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C009438:tetrandrine