Dopamine and ghrelin receptor co‐expression and interaction in the spinal defecation centers
| Autor: | Emily A. Whitfield, Linda J Fothergill, Andrew J. Syder, Jill Wykosky, Sebastian G.B. Furness, John B. Furness, Eun Ji Yoo, Mitchell T Ringuet, Andrea Fanjul, Ruslan V Pustovit |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Agonist medicine.medical_specialty Quinpirole Physiology medicine.drug_class Dopamine Receptor expression 03 medical and health sciences Pramipexole 0302 clinical medicine Piperidines Internal medicine Dopamine receptor D2 medicine Animals Humans Defecation Receptors Ghrelin Quinazolinones Spinal Cord Lateral Horn Receptors Dopamine D2 Endocrine and Autonomic Systems business.industry Gastroenterology Ghrelin Rats 030104 developmental biology Endocrinology Spinal Cord Dopamine receptor Dopamine Agonists Dopamine Antagonists Sulpiride Gastrointestinal Motility business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurogastroenterology & Motility. 33 |
| ISSN: | 1365-2982 1350-1925 |
| Popis: | BACKGROUND: Dopamine receptor 2 (DRD2) and ghrelin receptor (GHSR1a) agonists both stimulate defecation by actions at the lumbosacral defecation center. Dopamine is in nerve terminals surrounding autonomic neurons of the defecation center, whereas ghrelin is not present in the spinal cord. Dopamine at D2 receptors generally inhibits neurons, but at the defecation center, its effect is excitatory. METHODS: In vivo recording of defecation and colorectal propulsion was used to investigate interaction between DRD2 and GHSR1a. Localization studies were used to determine sites of receptor expression in rat and human spinal cord. KEY RESULTS: Dopamine, and the DRD2 agonist, quinpirole, directly applied to the lumbosacral cord, caused defecation. The effect of intrathecal dopamine was inhibited by the GHSR1a antagonist, YIL781, given systemically, but YIL781 was not an antagonist at DRD2. The DRD2 agonist, pramipexole, administered systemically caused colorectal propulsion that was prevented when the pelvic nerves were cut. Drd2 and Ghsr were expressed together in autonomic preganglionic neurons at the level of the defecation centers in rat and human. Behaviorally induced defecation (caused by water avoidance stress) was reduced by the DRD2 antagonist, sulpiride. We had previously shown it is reduced by YIL781. CONCLUSIONS AND INFERENCES: Our observations imply that dopamine is a transmitter of the defecation pathways whose actions are exerted through interacting dopamine (D2) and ghrelin receptors on lumbosacral autonomic neurons that project to the colorectum. The results explain the excitation by dopamine agonists and the conservation of GHSR1a in the absence of ghrelin. |
| Databáze: | OpenAIRE |
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