title: Diarrhetic effect of okadaic acid could be related with its neuronal action: Changes in neuropeptide Y.
abstract: Okadaic acid (OA) and dinophysistoxins (DTXs) are a group of marine toxins that cause diarrheic shellfish poisoning (DSP) in humans and animals. These compounds are produced by dinoflagellates of the Prorocentrum and Dinophysis genera and can accumulate in filter-feeding bivalves, posing a serious health risk for shellfish consumers. The enteric nervous system (ENS) plays a crucial role in the regulation of the gastrointestinal tract. In addition, neuropeptides produced by ENS affects the epithelial barrier functions. In the present work we used a two-compartment human coculture model containing the SH-SY5Y neuroblastoma cell line and polarized colonic epithelial monolayers (Caco-2) to study the OA intestinal permeability. First, we have determined OA cytotoxicity and we have found that OA reduces the viability of SH-SY5Y in a dose-dependent way, even though DTX1 is 4 to 5 times more potent than OA. Besides DTX1 is 15 to 18 orders of magnitude more potent than OA in decreasing transepithelial electrical resistance (TEER) of caco-2 cells without inducing cytotoxicity. Permeability assays indicate that OA cross the monolayer and modulates the neuropeptide Y (NPY) secretion by neuroblastoma cells. This NPY also affects the permeability of OA. This offers a novel approach to establish the influence of OA neuronal action on their diarrheic effects through a cross talk between ENS and intestine via OA induced NPY secretion. Therefore, the OA mechanisms of toxicity that were long attributed only to the inhibition of protein phosphatases, would require a reevaluation.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain. Electronic address: mcarmen.louzao@usc.es.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Louzao
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Fernández
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Abal
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Fraga
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vilariño
authors.affiliation: Departamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain.
authors.forename: Mercedes R
authors.initials: MR
authors.lastname: Vieytes
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain. Electronic address: luis.botana@usc.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced*; D017097:Electric Impedance; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D009478:Neuropeptide Y / Q000032:analysis*; D019319:Okadaic Acid / Q000633:toxicity* / Q000031:analogs & derivatives; D011714:Pyrans / Q000633:toxicity
chemical_list: D009478:Neuropeptide Y; D011714:Pyrans; D019319:Okadaic Acid; C051904:dinophysistoxin 1
keywords: Caco-2; Dinophysistoxin-1; Intestinal permeability; Neuroblastoma cells; Neuropeptide Y; Okadaic acid