{"doi":"10.1101/2024.12.14.628386","title":"The pyrethroid insecticide deltamethrin disrupts neuropeptide and monoamine signaling pathways in the gastrointestinal tract","abstract":"Abstract Enteroendocrine cells (EECs) are a rare cell type of the intestinal epithelium. Various subtypes of EECs produce distinct repertoires of monoamines and neuropeptides which modulate intestinal motility and other physiologies. EECs also possess neuron-like properties, suggesting a potential vulnerability to ingested environmental neurotoxicants. One such group of toxicants are pyrethroids, a class of prevalent insecticides used residentially and agriculturally. Pyrethroids agonize voltage-gated sodium channels (VGSCs), inducing neuronal excitotoxicity, and affect the function of monoamine-producing neurons. Given their anatomical location at the interface with the environment and their expression of VGSCs, EECs likely represent a vulnerable cell-type to oral pyrethroid exposure. In this study, we used the EEC cell line, STC-1 cells, to evaluate the effects of the common pyrethroid deltamethrin on the functional status of EECs. We find that deltamethrin impacts both expression of serotonergic pathways and inhibits the adrenergic-evoked release of an EEC hormone, GLP-1, in vitro . In a mouse model of oral exposure, we found that deltamethrin induced an acute, yet transient, loss of intestinal motility, in both fed and fasted conditions. This constipation phenotype was accompanied by a significant decrease in peripheral serotonin production and an inhibition of nutrient-evoked intestinal hormone release. Together, these data demonstrate that deltamethrin alters monoaminergic signaling pathways in EECs and regulates intestinal motility. This work demonstrates a mechanistic link between pyrethroid exposure and intestinal impacts relevant to pyrethroid-associated diseases, including inflammatory bowel disease, neurodegenerative disease, and metabolic disorders.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":507808,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":948082,"name":"Ian N Krout","orcid":"0000-0002-4711-8757","position":1,"is_corresponding":false},{"id":1359902,"name":"Sabra Mouhi","orcid":null,"position":2,"is_corresponding":false},{"id":317757,"name":"Jianjun Chang","orcid":"0000-0001-6707-1944","position":3,"is_corresponding":false},{"id":317756,"name":"Sean D. Kelly","orcid":"0000-0001-6625-5258","position":4,"is_corresponding":false},{"id":397967,"name":"W. Michael Caudle","orcid":"0000-0003-4374-2031","position":5,"is_corresponding":false},{"id":228763,"name":"Timothy R. Sampson","orcid":"0000-0002-2486-8766","position":6,"is_corresponding":false},{"id":1359606,"name":"Anna White","orcid":"0000-0002-9261-9868","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:11:06.395600Z","pmid":"39763966","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}