Serotonin involvement in okadaic acid-induced diarrhoea in vivo

M Carmen Louzao,Carmen Vale,Toshiyuki Suzuki,Cristina Carrera,Paula Abal,Luis M Botana,Celia Costas,Natalia Vilariño,Ryuichi Watanabe,Andrea Boente-Juncal,Mercedes R Vieytes

doi:10.1007/s00204-021-03095-z

M Carmen Louzao, Carmen Vale + Show 9 more

Open Access

https://doi.org/10.1007/s00204-021-03095-z

Copy DOI

Abstract

The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms including nausea, vomiting and diarrhoea. These phycotoxins are Ser/Thr phosphatase inhibitors, which produce hyperphosphorylation in cellular proteins. However, this inhibition does not fully explain the symptomatology reported and other targets could be relevant to the toxicity. Previous studies have indicated a feasible involvement of the nervous system. We performed a set of in vivo approaches to elucidate whether neuropeptide Y (NPY), Peptide YY (PYY) or serotonin (5-HT) was implicated in the early OA-induced diarrhoea. Fasted Swiss female mice were administered NPY, PYY(3–36) or cyproheptadine intraperitoneal prior to oral OA treatment (250 µg/kg). A non-significant delay in diarrhoea onset was observed for NPY (107 µg/kg) and PYY(3–36) (1 mg/kg) pre-treatment. On the contrary, the serotonin antagonist cyproheptadine was able to block (10 mg/kg) or delay (0.1 and 1 mg/kg) diarrhoea onset suggesting a role of 5-HT. This is the first report of the possible involvement of serotonin in OA-induced poisoning.

Highlights

Okadaic acid (OA) group of toxins comprise polyether fatty acids synthetized by dinoflagellates of the genera Prorocentrum and Dinophysis
Gathering the variety of pathophysiologic mechanisms resulting in diarrhoea and the important role of the Enteric Nervous System (ENS), we studied if OA-caused diarrhoea involves alteration of intestinal hormones (PYY) and/or neurotransmitters (5-HT and Neuropeptide Y (NPY))
Clinical signs were noted at 1 h for 100 μg/kg OA treatment, being absent at 3 h

Summary

Introduction

Okadaic acid (OA) group of toxins comprise polyether fatty acids synthetized by dinoflagellates of the genera Prorocentrum and Dinophysis. OA and related compounds enter the food chain reaching humans through toxin-containing seafood ingestion causing diarrhoeic shellfish poisoning (DSP) (Yasumoto et al 1978). Previous studies have revealed that OA inhibits serine/ threonine protein phosphatases (PPs) 1, 2A, 4, 5 and 6 activity (Bialojan and Takai 1988; Brewis et al 1993; Chen et al 1994; Prickett and Brautigan 2006). PPs remove a phosphate group from the phosphorylated amino acid residue of a wide variety of proteins (Yadav et al 2017), meaning disturbance in their activity can modify downstream cellular pathways. During the last decade, it has been discussed whether OA-exerted effects are fully explained by its PP inhibition (Espina et al 2010; Munday 2013)

Objectives

Methods

Results

Discussion

Conclusion