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Dopamine regulates colonic glial cell-derived neurotrophic factor secretion through cholinergic dependent and independent pathways.
Zhang, Xiao-Li; Sun, Qi; Quan, Zhu-Sheng; Wu, Liang; Liu, Zi-Ming; Xia, Yan-Qi; Wang, Qian-Yi; Zhang, Yue; Zhu, Jin-Xia.
Afiliação
  • Zhang XL; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Sun Q; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Quan ZS; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Wu L; Endoscopy Center, Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Liu ZM; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Xia YQ; Grade 2020 Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Wang QY; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Zhang Y; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • Zhu JX; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Br J Pharmacol ; 181(3): 413-428, 2024 02.
Article em En | MEDLINE | ID: mdl-37614042
ABSTRACT
BACKGROUND AND

PURPOSE:

Glial cell-derived neurotrophic factor (GDNF) maintains gut homeostasis. Dopamine promotes GDNF release in astrocytes. We investigated the regulation by dopamine of colonic GDNF secretion. EXPERIMENTAL

APPROACH:

D1 receptor knockout (D1 R-/- ) mice, adeno-associated viral 9-short hairpin RNA carrying D2 receptor (AAV9-shD2 R)-treated mice, 6-hydroxydopamine treated (6-OHDA) rats and primary enteric glial cells (EGCs) culture were used. Incubation fluid from colonic submucosal plexus and longitudinal muscle myenteric plexus were collected for GDNF and ACh measurements. KEY

RESULTS:

D2 receptor-immunoreactivity (IR), but not D1 receptor-IR, was observed on EGCs. Both D1 receptor-IR and D2 receptor-IR were co-localized on cholinergic neurons. Low concentrations of dopamine induced colonic GDNF secretion in a concentration-dependent manner, which was mimicked by the D1 receptor agonist SKF38393, inhibited by TTX and atropine and eliminated in D1 R-/- mice. SKF38393-induced colonic ACh release was absent in D1 R-/- mice. High concentrations of dopamine suppressed colonic GDNF secretion, which was mimicked by the D2 receptor agonist quinpirole, and absent in AAV-shD2 R-treated mice. Quinpirole decreased GDNF secretion by reducing intracellular Ca2+ levels in primary cultured EGCs. Carbachol ( ACh analogue) promoted the release of GDNF. Quinpirole inhibited colonic ACh release, which was eliminated in the AAV9-shD2 R-treated mice. 6-OHDA treated rats with low ACh and high dopamine content showed decreased GDNF content and increased mucosal permeability in the colon. CONCLUSION AND IMPLICATIONS Low concentrations of dopamine promote colonic GDNF secretion via D1 receptors on cholinergic neurons, whereas high concentrations of dopamine inhibit GDNF secretion via D2 receptors on EGCs and/or cholinergic neurons.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dopamina / Fator Neurotrófico Derivado de Linhagem de Célula Glial Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dopamina / Fator Neurotrófico Derivado de Linhagem de Célula Glial Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China