The role of hypothalamic Orexin-A in stress-induced gastric dysmotility: An agonistic interplay with corticotropin releasing factor


SİNEN O., Akçalı İ., Akkan S. S., BÜLBÜL M.

Neurogastroenterology and Motility, cilt.36, sa.1, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1111/nmo.14719
  • Dergi Adı: Neurogastroenterology and Motility
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Food Science & Technology Abstracts, MEDLINE
  • Anahtar Kelimeler: acute restraint stress, CRF, gastric emptying, microdialysis, orexin-A
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Background: Central Orexin-A (OXA) modulates gastrointestinal (GI) functions and stress response. This study aimed to investigate whether OXA and CRF interact at hypothalamic level. Methods: Solid gastric emptying (GE), fecal output (FO), plasma corticosterone (CORT), and postprandial antro-pyloric motility were assessed in rats that underwent acute restraint stress (ARS) and pretreated with central OX1R and/or CRF receptor antagonists SB-334867 and alpha-helical CRF9,41. Microdialysis was performed to assess ARS-induced release of OXA and CRF in PVN and LHA, respectively. Immunofluorescence labeling was performed to detect the stress-induced changes in OXA and to assess the hypothalamic distribution of OX1R and CRF1/2 receptors. ARS-induced c-Fos immunoreactivity was evaluated in PVN and LHA of rats received OX1R and CRF receptor antagonists. Key Results: ARS delayed GE by disturbing the coordination of antro-pyloric contractions while stimulating FO and CORT secretion. ARS-induced alterations in GE, FO, plasma CORT, and antro-pyloric motility were attenuated by OX1R and/or CRF receptor antagonists, however, these changes were completely restored in rats received both antagonists. ARS stimulated release of OXA and CRF which were significantly attenuated by α-CRF9,41 and SB-334867, respectively. The OX1R was detected in CRF-immunoreactive cells, whereas dense expression of CRF2 receptor but not CRF1 was observed in LHA. ARS remarkably increased OXA immunoreactivity in LHA. ARS-induced c-Fos expression in LHA and PVN was abolished by α-CRF9,41 and SB-334867, respectively. Conclusions & Inferences: Our findings suggest a reciprocal contribution of OXA and CRF which seems to be involved in the mediation of stress-induced alterations in neuroendocrine and GI motor functions.