title: Ciguatoxin-induced catecholamine secretion in bovine chromaffin cells: mechanism of action and reversible inhibition by brevenal.
abstract: Ciguatoxin (P-CTX-1B) from the dinoflagellate Gambierdiscus toxicus, belongs to the family of polyether neurotoxins responsible for the neurological poisoning disorder ciguatera. Although it is the most widespread marine-borne disease affecting humans, there is no current FDA-approved treatment available except for symptomatic therapies. In this paper, we report that P-CTX-1B promotes catecholamine secretion from bovine chromaffin cells, an effect that is insensitive to concomitant activation of capacitative Ca(2+) entry. Moreover, we confirm that brevenal, a polyether from the dinoflagellate Karenia brevis, blocks P-CTX-1B-induced catecholamine secretion. This effect is partially reversible. Our results therefore raise the prospect of finding functional antagonists for P-CTX-1B that could be useful for the treatment of ciguatera.
authors.affiliation: Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland, St Lucia Campus, Brisbane, Australia.
authors.forename: Truong D
authors.initials: TD
authors.lastname: Nguyen-Huu
authors.forename: César
authors.initials: C
authors.lastname: Mattei
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wen
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Bourdelais
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
authors.forename: Evelyne
authors.initials: E
authors.lastname: Benoit
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Baden
authors.forename: Jordi
authors.initials: J
authors.lastname: Molgó
authors.forename: Frédéric A
authors.initials: FA
authors.lastname: Meunier
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D002922:Ciguatoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004987:Ethers / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D004987:Ethers; D011108:Polymers; C489035:brevenal (polyether); D002922:Ciguatoxins