Evidence for dopamine production and distribution of dopamine D2 receptors in the equine gastrointestinal mucosa and pancreas

Nicolas C. Galinelli, Nicholas J. Bamford,Melody A. de Laat,Martin N. Sillence,Patricia A. Harris,Simon R. Bailey

PLOS ONE(2024)

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摘要
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-2 receptors in tissue sections. Additional immunostaining for glucagon, insulin and chromogranin A was performed to identify alpha cells, beta cells and enteroendocrine cells, respectively. Gastric parietal cells expressed both TH and D-2 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-2 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-2 receptor. In pancreatic islets, TH was present in alpha cells, while D-2 receptors were strongly expressed in beta cells and variably expressed in alpha 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.
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