TY - JOUR
T1 - Environmental levels of carbaryl impair zebrafish larvae behaviour
T2 - The potential role of ADRA2B and HTR2B
AU - Faria, Melissa
AU - Bellot, Marina
AU - Bedrossiantz, Juliette
AU - Ramírez, Jonathan Ricardo Rosas
AU - Prats, Eva
AU - Garcia-Reyero, Natalia
AU - Gomez-Canela, Cristian
AU - Mestres, Jordi
AU - Rovira, Xavier
AU - Barata, Carlos
AU - Oliván, Leobardo Manuel Gómez
AU - Llebaria, Amadeu
AU - Raldua, Demetrio
N1 - Funding Information:
This work was supported by “Agencia Estatal de Investigación” from the Spanish Ministry of Science and Innovation (project PID2020-113371RB-C21 ), IDAEA-CSIC , Severo Ochoa Centre of Excellence ( CEX2018-000794-S ), which financed M.F. with Severo Ochoa funds. Juliette Bedrossiantz was supported by a PhD grant ( PRE2018-083513 ) co-financied by the Spanish Government and the European Social Fund (ESF). This work was supported by Ministerio de Ciencia e Innovación , Agencia Estatal de Investigación and ERDF-FEDER European Fund (projects CTQ2017-89222-R and PID2020-120499RB-I00 ) and by the Catalan Government ( 2017 SGR 1604 and 2017-SGR-1807 ) to AL. XR research was financed by the Spanish Ministry of Economy, Industry and Competitiveness ( SAF2015-74132-JIN ). We thank Dr. Kees Jalink (The Netherlands Cancer Institute, Amsterdam, the Netherlands) for providing the plasmids encoding for the Epac-S H188 biosensor and Dr. Karen Martinez (University of Copenhagen, Copenhagen, Denmark) for providing the HEK 293 SNAP-β1AR). The findings of this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents.
Funding Information:
This work was supported by ?Agencia Estatal de Investigaci?n? from the Spanish Ministry of Science and Innovation (project PID2020-113371RB-C21), IDAEA-CSIC, Severo Ochoa Centre of Excellence (CEX2018-000794-S), which financed M.F. with Severo Ochoa funds. Juliette Bedrossiantz was supported by a PhD grant (PRE2018-083513) co-financied by the Spanish Government and the European Social Fund (ESF). This work was supported by Ministerio de Ciencia e Innovaci?n, Agencia Estatal de Investigaci?n and ERDF-FEDER European Fund (projects CTQ2017-89222-R and PID2020-120499RB-I00) and by the Catalan Government (2017 SGR 1604 and 2017-SGR-1807) to AL. XR research was financed by the Spanish Ministry of Economy, Industry and Competitiveness (SAF2015-74132-JIN). We thank Dr. Kees Jalink (The Netherlands Cancer Institute, Amsterdam, the Netherlands) for providing the plasmids encoding for the Epac-SH188 biosensor and Dr. Karen Martinez (University of Copenhagen, Copenhagen, Denmark) for providing the HEK 293 SNAP-?1AR). The findings of this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents.
Publisher Copyright:
© 2022 The Authors
PY - 2022/6/5
Y1 - 2022/6/5
N2 - The insecticide carbaryl is commonly found in indirectly exposed freshwater ecosystems at low concentrations considered safe for fish communities. In this study, we showed that after only 24 h of exposure to environmental concentrations of carbaryl (0.066–660 ng/L), zebrafish larvae exhibit impairments in essential behaviours. Interestingly, the observed behavioural effects induced by carbaryl were acetylcholinesterase-independent. To elucidate the molecular initiating event that resulted in the observed behavioural effects, in silico predictions were followed by in vitro validation. We identified two target proteins that potentially interacted with carbaryl, the α2B adrenoceptor (ADRA2B) and the serotonin 2B receptor (HTR2B). Using a pharmacological approach, we then tested the hypothesis that carbaryl had antagonistic interactions with both receptors. Similar to yohimbine and SB204741, which are prototypic antagonists of ADRA2B and HTR2B, respectively, carbaryl increased the heart rate of zebrafish larvae. When we compared the behavioural effects of a 24-h exposure to these pharmacological antagonists with those of carbaryl, a high degree of similarity was found. These results strongly suggest that antagonism of both ADRA2B and HTR2B is the molecular initiating event that leads to adverse outcomes in zebrafish larvae that have undergone 24 h of exposure to environmentally relevant levels of carbaryl.
AB - The insecticide carbaryl is commonly found in indirectly exposed freshwater ecosystems at low concentrations considered safe for fish communities. In this study, we showed that after only 24 h of exposure to environmental concentrations of carbaryl (0.066–660 ng/L), zebrafish larvae exhibit impairments in essential behaviours. Interestingly, the observed behavioural effects induced by carbaryl were acetylcholinesterase-independent. To elucidate the molecular initiating event that resulted in the observed behavioural effects, in silico predictions were followed by in vitro validation. We identified two target proteins that potentially interacted with carbaryl, the α2B adrenoceptor (ADRA2B) and the serotonin 2B receptor (HTR2B). Using a pharmacological approach, we then tested the hypothesis that carbaryl had antagonistic interactions with both receptors. Similar to yohimbine and SB204741, which are prototypic antagonists of ADRA2B and HTR2B, respectively, carbaryl increased the heart rate of zebrafish larvae. When we compared the behavioural effects of a 24-h exposure to these pharmacological antagonists with those of carbaryl, a high degree of similarity was found. These results strongly suggest that antagonism of both ADRA2B and HTR2B is the molecular initiating event that leads to adverse outcomes in zebrafish larvae that have undergone 24 h of exposure to environmentally relevant levels of carbaryl.
KW - ADRA2B
KW - Acetylcholinesterase
KW - Behaviour
KW - Carbaryl
KW - HTR2B
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85125530933&partnerID=8YFLogxK
UR - http://hdl.handle.net/20.500.14342/4459
U2 - 10.1016/j.jhazmat.2022.128563
DO - 10.1016/j.jhazmat.2022.128563
M3 - Article
C2 - 35248961
AN - SCOPUS:85125530933
SN - 0304-3894
VL - 431
JO - Journal of Hazardous Materials
JF - Journal of Hazardous Materials
M1 - 128563
ER -