Ciguatoxin-induced catecholamine secretion in bovine chromaffin cells: mechanism of action and reversible inhibition by brevenal.
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.
Nguyen-Huu
Truong D
TD
Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland, St Lucia Campus, Brisbane, Australia.
Mattei
César
C
Wen
Peter J
PJ
Bourdelais
Andrea J
AJ
Lewis
Richard J
RJ
Benoit
Evelyne
E
Baden
Daniel G
DG
Molgó
Jordi
J
Meunier
Frédéric A
FA
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*
D002395:Catecholamines; D004987:Ethers; D011108:Polymers; C489035:brevenal (polyether); D002922:Ciguatoxins