{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:18:40Z","timestamp":1768519120786,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,17]]},"group-title":"Pharmacology and Toxicology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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,\n                  <jats:italic>in vitro<\/jats:italic>\n                  . 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.\n                <\/jats:p>","DOI":"10.1101\/2024.12.14.628386","type":"posted-content","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T16:45:48Z","timestamp":1734713148000},"source":"Crossref","is-referenced-by-count":0,"title":["The pyrethroid insecticide deltamethrin disrupts neuropeptide and monoamine signaling pathways in the gastrointestinal tract"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-9868","authenticated-orcid":false,"given":"Alexandria C.","family":"White","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4711-8757","authenticated-orcid":false,"given":"Ian N.","family":"Krout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6891-8356","authenticated-orcid":false,"given":"Sabra","family":"Mouhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean D.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-2031","authenticated-orcid":false,"given":"W. Michael","family":"Caudle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2486-8766","authenticated-orcid":false,"given":"Timothy R.","family":"Sampson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024122323435372000_2024.12.14.628386v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00344-4"},{"key":"2024122323435372000_2024.12.14.628386v1.2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78512"},{"key":"2024122323435372000_2024.12.14.628386v1.3","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00428"},{"key":"2024122323435372000_2024.12.14.628386v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.11.011"},{"key":"2024122323435372000_2024.12.14.628386v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.032"},{"key":"2024122323435372000_2024.12.14.628386v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18259-0"},{"key":"2024122323435372000_2024.12.14.628386v1.7","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-015-0051-0"},{"key":"2024122323435372000_2024.12.14.628386v1.8","unstructured":"ATSDR. 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