Department of Physiology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
Neurogastroenterol Motil. 2024 Jan;36(1):e14719. doi: 10.1111/nmo.14719. Epub 2023 Dec 17.
Central Orexin-A (OXA) modulates gastrointestinal (GI) functions and stress response. This study aimed to investigate whether OXA and CRF interact at hypothalamic level.
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 CRF . 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.
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-CRF 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-CRF 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.
中枢食欲素-A（OXA）调节胃肠道（GI）功能和应激反应。本研究旨在探讨 OXA 和 CRF 是否在下丘脑水平相互作用。
通过急性束缚应激（ARS）评估大鼠的固体胃排空（GE）、粪便排出量（FO）、血浆皮质酮（CORT）和餐后胃幽门运动，并分别用中枢 OX1R 和/或 CRF 受体拮抗剂 SB-334867 和α-螺旋 CRF 预处理。通过微透析评估 ARS 诱导的 PVN 和 LHA 中 OXA 和 CRF 的释放。免疫荧光标记用于检测 OXA 的应激诱导变化，并评估下丘脑 OX1R 和 CRF1/2 受体的分布。评估接受 OX1R 和 CRF 受体拮抗剂的大鼠在 PVN 和 LHA 中 ARS 诱导的 c-Fos 免疫反应性。
ARS 通过干扰胃幽门收缩的协调来延迟 GE，同时刺激 FO 和 CORT 分泌。GE、FO、血浆 CORT 和胃幽门运动的 ARS 诱导变化被 OX1R 和/或 CRF 受体拮抗剂减弱，但在接受两种拮抗剂的大鼠中这些变化完全恢复。ARS 刺激 OXA 和 CRF 的释放，分别被 α-CRF 和 SB-334867 显著减弱。OX1R 存在于 CRF 免疫反应性细胞中，而 LHA 中观察到密集表达 CRF2 受体而不是 CRF1。ARS 显著增加了 LHA 中的 OXA 免疫反应性。ARS 诱导的 LHA 和 PVN 中的 c-Fos 表达分别被 α-CRF 和 SB-334867 消除。
我们的发现表明 OXA 和 CRF 之间存在相互贡献，这似乎参与了应激诱导的神经内分泌和 GI 运动功能变化的调节。
