tailieunhanh - Báo cáo khoa học: Weak toxin WTX from Naja kaouthia cobra venom interacts with both nicotinic and muscarinic acetylcholine receptors

Iodinated [ 125 I] weak toxin from Naja kaouthia(WTX) cobra venom was injected into mice, and organ-specific binding was monitored. Relatively high levels of [ 125 I]WTX were detected in the adrenal glands. Rat adrenal membranes were therefore used for analysis of [ 125 I]WTX-binding sites. | ỊFEBS Journal Weak toxin WTX from Naja kaouthia cobra venom interacts with both nicotinic and muscarinic acetylcholine receptors Dmitry Yu. Mordvintsev1 Yakov L. Polyak1 Dmitry I. Rodionov1 Jan Jakubik2 Vladimir Dolezal2 Evert Karlsson3 Victor I. Tsetlin1 and Yuri N. Utkin1 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS Moscow Russia 2 Institute of Physiology Prague Czech Republic 3 Institute of Biochemistry and Organic Chemistry Uppsala Sweden Keywords muscarinic acetylcholine receptor nicotinic acetylcholine receptor snake venom weak neurotoxin Correspondence Y. N. Utkin Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS ul. Miklukho-Maklaya 16 10 Moscow 117997 Russia Fax 7 495 335 57 33 Tel 007 495 336 65 22 E-mailutkin@ Present addresses Max-Planck-Institute fur Kohlenforschung Mulheim an der Ruhr Germany fMcGillUniversity Montreal Canada Received 16 December 2008 revised 25 May 2009 accepted 7 July 2009 doi Iodinated 125I weak toxin from Naja kaouthia WTX cobra venom was injected into mice and organ-specific binding was monitored. Relatively high levels of 125I WTX were detected in the adrenal glands. Rat adrenal membranes were therefore used for analysis of 125I WTX-binding sites. Specific 125I WTX binding was partially inhibited by both a-cobratoxin a blocker of the a7 and muscle-type nicotinic acetylcholine receptors nAChRs and by atropine an antagonist of the muscarinic acetylcholine receptor mAChR . Binding to rat adrenal nAChR had a Kd of IM and was inhibited by a-cobratoxin but not by a short-chain a-neurotoxin antagonist of the muscle-type nAChR suggesting a specific interaction with the a7-type nAChR. WTX binding was reduced not only by atropine but also by other muscarinic agents oxotremorine and muscarinic toxins from Dendroaspis angusticeps indicating an interaction with mAChR. This interaction was further characterized using individual subtypes of human mAChRs expressed in