{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:13:14Z","timestamp":1793261594048,"version":"4.5.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LP180101000"],"award-info":[{"award-number":["LP180101000"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Boehringer Ingelheim Vetmedica GMBH"},{"name":"Mars Petcare UK"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Insulin dysregulation in horses is characterised by hyperinsulinaemia and\/or tissue insulin resistance and is associated with increased risk of laminitis. There is growing evidence in other species that dopamine attenuates insulin release from the pancreas; however, this has yet to be examined in horses. The present study aimed to identify whether there are cells capable of producing or responding to dopamine within the equine gastrointestinal mucosa and pancreas. Tissue samples were collected from the stomach, small and large intestines, and pancreas of six mature horses following euthanasia. Samples of stomach contents and faeces were also collected. Immunohistochemistry was performed to identify tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine production, and dopamine D<jats:sub>2<\/jats:sub> receptors in tissue sections. Additional immunostaining for glucagon, insulin and chromogranin A was performed to identify \u03b1 cells, \u03b2 cells and enteroendocrine cells, respectively. Gastric parietal cells expressed both TH and D<jats:sub>2<\/jats:sub> receptors, indicating that they are capable of both producing and responding to dopamine. Dopamine was quantified in stomach contents and faeces by high-performance liquid chromatography with electrochemical detection, with similar concentrations found at both sites. Dopamine D<jats:sub>2<\/jats:sub> receptors were expressed in duodenal epithelial cells but not more distally. A subset of enteroendocrine cells, located sporadically along the gastrointestinal tract, were found to be immunopositive for the D<jats:sub>2<\/jats:sub> receptor. In pancreatic islets, TH was present in \u03b1 cells, while D<jats:sub>2<\/jats:sub> receptors were strongly expressed in \u03b2 cells and variably expressed in \u03b1 cells. These findings are consistent with studies of other species; however, dynamic studies are required to further elucidate the role of dopamine in the modulation of insulin and glucagon secretion in horses. This descriptive study provides preliminary evidence for a potential role of dopamine to act as a paracrine messenger in the gastrointestinal mucosa and endocrine pancreas of horses.<\/jats:p>","DOI":"10.1371\/journal.pone.0298660","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:27:38Z","timestamp":1709058458000},"page":"e0298660","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evidence for dopamine production and distribution of dopamine D2 receptors in the equine gastrointestinal mucosa and pancreas"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5915-1159","authenticated-orcid":true,"given":"Nicolas C.","family":"Galinelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7675-9126","authenticated-orcid":true,"given":"Nicholas J.","family":"Bamford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody A.","family":"de Laat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin N.","family":"Sillence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9348-5497","authenticated-orcid":true,"given":"Simon R.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"issue":"2","key":"pone.0298660.ref001","first-page":"335","volume":"33","author":"AE Durham","year":"2019","journal-title":"ECEIM consensus statement on equine metabolic syndrome."},{"issue":"1","key":"pone.0298660.ref002","first-page":"103","volume":"46","author":"N Frank","year":"2014","journal-title":"Insulin dysregulation."},{"issue":"4","key":"pone.0298660.ref003","doi-asserted-by":"crossref","first-page":"e0123197","DOI":"10.1371\/journal.pone.0123197","article-title":"Dopamine Modulates Insulin Release and Is Involved in the Survival of Rat Pancreatic Beta Cells.","volume":"10","author":"MJ Garcia Barrado","year":"2015","journal-title":"PLOS ONE."},{"issue":"1","key":"pone.0298660.ref004","first-page":"43","volume":"41","author":"S Chaudhry","year":"2016","journal-title":"Gastrointestinal dopamine as an anti-incretin and its possible role in bypass surgery as therapy for type 2 diabetes with associated obesity."},{"issue":"9","key":"pone.0298660.ref005","first-page":"1946","article-title":"Dopamine negatively regulates insulin secretion through activation of D1-D2","volume":"71","author":"F Uefune","year":"2022","journal-title":"receptor heteromer"},{"key":"pone.0298660.ref006","doi-asserted-by":"crossref","first-page":"889888","DOI":"10.3389\/fvets.2022.889888","article-title":"Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses.","volume":"9","author":"CMM Loos","year":"2022","journal-title":"Front Vet Sci."},{"issue":"1","key":"pone.0298660.ref007","first-page":"597","volume":"35","author":"J Delarocque","year":"2021","journal-title":"Metabolic changes induced by oral glucose tests in horses and their diagnostic use."},{"issue":"4","key":"pone.0298660.ref008","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1365-2885.1988.tb00195.x","article-title":"Biphasic disruption of fasting equine gut motility by dopamine\u2013a preliminary study","volume":"11","author":"NJ King","year":"1988","journal-title":"Journal of veterinary pharmacology therapeutics"},{"issue":"2, Part 1","key":"pone.0298660.ref009","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0016-5085(78)90800-4","article-title":"Inhibition of gastrin secretion by sulpiride treatment in duodenal ulcer patients","volume":"74","author":"R Caldara","year":"1978","journal-title":"Gastroenterology"},{"issue":"14","key":"pone.0298660.ref010","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1111\/bph.15047","article-title":"Source of dopamine in gastric juice and luminal dopamine-induced duodenal bicarbonate secretion via apical dopamine D(2) receptors.","volume":"177","author":"XY Feng","year":"2020","journal-title":"Br J Pharmacol"},{"issue":"9","key":"pone.0298660.ref011","first-page":"2070","volume":"25","author":"ZJ Farino","year":"2020","journal-title":"New roles for dopamine D2 and D3 receptors in pancreatic beta cell insulin secretion."},{"issue":"44","key":"pone.0298660.ref012","doi-asserted-by":"crossref","first-page":"36824","DOI":"10.1074\/jbc.M505560200","article-title":"Dopamine D2-like receptors are expressed in pancreatic beta cells and mediate inhibition of insulin secretion","volume":"280","author":"B Rubi","year":"2005","journal-title":"The Journal of biological chemistry"},{"issue":"1","key":"pone.0298660.ref013","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbrc.2011.11.084","article-title":"Cellular localization of dopamine receptors in the gastric mucosa of rats","volume":"417","author":"Q Wang","year":"2012","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"6","key":"pone.0298660.ref014","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1523\/JNEUROSCI.3982-03.2004","article-title":"Enteric dopaminergic neurons: definition, developmental lineage, and effects of extrinsic denervation","volume":"24","author":"ZS Li","year":"2004","journal-title":"J Neurosci"},{"issue":"7","key":"pone.0298660.ref015","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1113\/jphysiol.2007.149815","article-title":"Activity-dependent regulation of tyrosine hydroxylase expression in the enteric nervous system","volume":"586","author":"J Chevalier","year":"2008","journal-title":"The Journal of Physiology"},{"key":"pone.0298660.ref016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1196\/annals.1294.001","article-title":"The \"normal\" endocrine cell of the gut: changing concepts and new evidences.","volume":"1014","author":"G Rindi","year":"2004","journal-title":"Ann N Y Acad Sci"},{"key":"pone.0298660.ref017","first-page":"365","volume":"21","author":"K Schmid","year":"1989","journal-title":"An immunological study on chromogranin A and B in human endocrine and nervous tissues"},{"issue":"5","key":"pone.0298660.ref018","first-page":"354","article-title":"Analysis of the Adrenal Gland Is Useful for Evaluating Pathology of the Peripheral Autonomic Nervous System in Lewy Body Disease. Journal of Neuropathology &","volume":"66","author":"Y Fumimura","year":"2007","journal-title":"Experimental Neurology"},{"key":"pone.0298660.ref019","author":"H-D Dellman","journal-title":"Veterinary histology: an outline text-atlas1972"},{"issue":"11","key":"pone.0298660.ref020","first-page":"G1288","volume":"303","author":"Y Asano","year":"2012","journal-title":"Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice."},{"issue":"5","key":"pone.0298660.ref021","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1472-8206.1993.tb00237.x","article-title":"Dopamine formation, from its immediate precursor 3, 4\u2010dihydroxyphenylalanine, along the rat digestive tract","volume":"7","author":"M Vieira\u2010Coelho","year":"1993","journal-title":"Fundamental & clinical pharmacology"},{"issue":"11","key":"pone.0298660.ref022","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1210\/jcem.82.11.4339","article-title":"Substantial production of dopamine in the human gastrointestinal tract","volume":"82","author":"G Eisenhofer","year":"1997","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"3\u20135","key":"pone.0298660.ref023","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0928-4257(97)89493-4","article-title":"Dopaminergic characteristics of isolated parietal cells from rats","volume":"91","author":"B Hunyady","year":"1997","journal-title":"Journal of Physiology-Paris"},{"issue":"5","key":"pone.0298660.ref024","first-page":"336","volume":"67","author":"\u00c9 Mezey","year":"1998","journal-title":"Dopamine produced by the stomach may act as a paracrine\/autocrine hormone in the rat."},{"issue":"4","key":"pone.0298660.ref025","first-page":"739","volume":"43","author":"K Hashimoto","year":"1971","journal-title":"Effect of dopamine on pancreatic secretion in the dog."},{"key":"pone.0298660.ref026","first-page":"1153","volume":"35","author":"GB Glavin","year":"1990","journal-title":"sciences. Dopamine in gastrointestinal disease"},{"issue":"4","key":"pone.0298660.ref027","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/BF01536330","article-title":"Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients","volume":"34","author":"DE Hernandez","year":"1989","journal-title":"Digestive diseases and sciences"},{"key":"pone.0298660.ref028","first-page":"221","author":"R Wall","year":"2014","journal-title":"Bacterial neuroactive compounds produced by psychobiotics"},{"key":"pone.0298660.ref029","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1002\/cphy.c170047","article-title":"Distribution and Stimulus Secretion Coupling of Enteroendocrine Cells along the Intestinal Tract.","author":"AE Adriaenssens","year":"2018","journal-title":"Comprehensive Physiology"},{"issue":"1","key":"pone.0298660.ref030","first-page":"185","volume":"170","author":"NW Bellono","year":"2017","journal-title":"Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways"},{"issue":"2","key":"pone.0298660.ref031","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.2042-3306.1984.tb01870.x","article-title":"Immunocytochemical distribution of endocrine cells in the gastrointestinal tract of the horse","volume":"16","author":"N Kitamura","year":"1984","journal-title":"Equine Vet J"},{"key":"pone.0298660.ref032","first-page":"83","article-title":"Crosstalk between insulin and dopamine signaling: A basis for the metabolic effects of antipsychotic drugs","author":"AI Nash","year":"2017","journal-title":"Journal of Chemical Neuroanatomy"},{"issue":"4","key":"pone.0298660.ref033","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1210\/en.2009-0996","article-title":"Disruption of the Dopamine D2 Receptor Impairs Insulin Secretion and Causes Glucose Intolerance","volume":"151","author":"I Garc\u00eda-Tornad\u00fa","year":"2010","journal-title":"Endocrinology"},{"issue":"651","key":"pone.0298660.ref034","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1136\/pgmj.56.651.11","article-title":"Effect of bromocriptine on maturity onset diabetes","volume":"56","author":"AH Barnett","year":"1980","journal-title":"Postgraduate Medical Journal"},{"issue":"3","key":"pone.0298660.ref035","first-page":"229","volume":"14","author":"G Rosati","year":"1976","journal-title":"Effects of long-term L-dopa therapy on carbohydrate metabolism in patients with Parkinson\u2019s disease"},{"issue":"12","key":"pone.0298660.ref036","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/j.bcp.2010.01.029","article-title":"The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the \u03b12-adrenergic receptors in beta cells","volume":"79","author":"JE de Leeuw van Weenen","year":"2010","journal-title":"Biochemical Pharmacology"},{"key":"pone.0298660.ref037","doi-asserted-by":"crossref","first-page":"101620","DOI":"10.1016\/j.mcp.2020.101620","article-title":"Metabogenomics reveals four candidate regions involved in the pathophysiology of Equine Metabolic Syndrome","volume":"53","author":"L Patterson Rosa","year":"2020","journal-title":"Molecular and Cellular Probes"},{"issue":"1","key":"pone.0298660.ref038","first-page":"27","article-title":"Immunohistochemical identification of the endocrine cells in the pancreatic islets of the camel, horse and cattle","volume":"19","author":"SA Hafez","year":"2015","journal-title":"Eur J Anat"},{"issue":"2","key":"pone.0298660.ref039","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2460\/ajvr.79.2.191","article-title":"Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance","volume":"79","author":"KM Newkirk","year":"2018","journal-title":"Am J Vet Res"},{"issue":"1","key":"pone.0298660.ref040","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41398-020-01171-z","article-title":"Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors.","volume":"11","author":"D Aslanoglou","year":"2021","journal-title":"Translational Psychiatry"},{"issue":"11","key":"pone.0298660.ref041","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1210\/me.2012-1226","article-title":"Dopamine Synthesis and D3 Receptor Activation in Pancreatic \u03b2-Cells Regulates Insulin Secretion and Intracellular [Ca2+] Oscillations.","volume":"26","author":"A Ustione","year":"2012","journal-title":"Molecular Endocrinology"},{"issue":"8","key":"pone.0298660.ref042","volume":"25","author":"D Aslanoglou","year":"2022","journal-title":"Dual pancreatic adrenergic and dopaminergic signaling as a therapeutic target of bromocriptine"},{"issue":"5","key":"pone.0298660.ref043","first-page":"400","volume":"18","author":"C Minimo","year":"1996","journal-title":"Role of computed quantitation of immunohistochemical staining of Ki-67 antigen in diagnosing ampullary lesions."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:28:34Z","timestamp":1709058514000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298660"}},"subtitle":[],"editor":[{"given":"Hanbing","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0298660","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,27]]}}}