Picrotoxin-mediated antagonism of alpha3beta4 and alpha7 acetylcholine receptors.
Picrotoxin (PTX) is a convulsant that antagonizes many inhibitory ligand-gated receptors. The mechanism of PTX block is believed to involve residues which line the pore in the second transmembrane domain (M2). The alpha(3)beta(4) and alpha(7) nicotinic acetylcholine receptors (nAChRs) have high homology to inhibitory LGICs in this M2 region and therefore could also be susceptible to block by PTX. Here, we report that PTX is an effective inhibitor at these nicotinic receptors (rat), with IC50 values of 96.1 +/- 5.5 and 194.9 +/- 19.2 microM for the alpha(3)beta(4) and alpha(7), respectively. These results provide insights into the structure-function relation of PTX-mediated antagonism in this family of ligand-activated receptors. Furthermore they should also be considered when employing PTX to selectively eliminate GABA- or glycine-mediated events.
Department of Neurobiology, University of Alabama at Birmingham School of Medicine, 1719 6th Ave South CIRC 410, Birmingham, AL 35294, USA.
Brian E
BE
Erkkila
David S
DS
Weiss
Virginia E
VE
Wotring
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism* / Q000502:physiology; D016415:Sequence Alignment; D014162:Transfection / Q000379:methods; D014982:Xenopus laevis
D002217:Carbachol; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D018756:GABA Antagonists; D010446:Peptide Fragments; D010852:Picrotoxin; D011978:Receptors, Nicotinic