Corticotropin‐Releasing Factor (CRF) and Glucocorticoids as Gastroprotective Components of Brain‐Gut Interactions in Stress
Authors: Filaretova Liudmila , Myazina Marina , Bagaeva Tatiana 
Published: November 2023

The brain and the gut interact through the brain‐gut axis. In the brain‐gut interaction the main endocrine role belongs to the hypothalamic‐pituitary‐adrenocortical (HPA) system, along with CRF. CRF is a central mediator of response to stress. Stress and CRF may alter the brain‐gut interactions leading to the development of gastrointestinal disorders, but stress and CRF may also play adaptive gastroprotective role. The results of our previous studies suggest that stress‐produced glucocorticoids are gastroprotective but not ulcerogenic ones. Here we investigated whether CRF, endogenous and exogenous, may protect the gastric mucosa against stress‐induced injury through involvement of glucocorticoids, the CRF receptor types 1 and 2 (CRF1 and CRF2 receptors). For this we examined the effects of CRF and CRF1 and CRF2 receptor antagonists on 3 h cold‐restraint‐induced gastric erosion as well as blood plasma corticosterone levels in 24 h fasted male rats. CRF (2.5 mg/kg, intraperitoneal, ip) or CRF vehicle was injected 30 min before the onset of cold‐restraint. The selective CRF1 receptor antagonist NBI 27914 (10 mg/kg, ip) and the selective CRF2 receptor antagonist astressin2‐B (50 mg/kg, ip) or its vehicles were injected 15 min before CRF or CRF vehicle as well as before the onset of cold‐restraint. Acute exposure to 3 h cold‐restraint caused gastric erosion formation and plasma corticosterone rise. Peripheral CRF injection markedly increased plasma corticosterone levels 15 and 30 min after the injection (before the onset of stress) and significantly suppressed the occurrence of gastric erosion induced by 3 h cold‐restraint. Cold‐restraint‐induced corticosterone rise was inhibited by NBI 27914 injection and these results confirm the critical role of CRF1 receptors in the activation of the HPA axis. NBI 27914 injection resulted in significant attenuation of gastroprotective effect of peripheral CRF. However, as there was no full prevention of gastroprotective action of CRF after NBI 27914 pretreatment, we also investigated the contribution of CRF2 receptors. Astressin2‐B injection significantly attenuated protective effect of peripheral CRF against gastric injury produced by cold‐restraint. Moreover, in experiments without CRF injection both NBI 27914 and astressin2‐B pretreatment before cold‐restain significantly aggravated gastric injury caused by cold‐restraind. The results obtained demonstrate that CRF (peripheral exogenous as well as endogenous one) may protect the gastric mucosa against cold‐restraint injury through involvement of glucocorticoids, CRF1 and CRF2 receptors. The data suggest that CRF and stress‐produced glucocorticoids are gastroprotective components of the brain‐gut axis in stress. The finding further support the idea that activation of the HPA axis is gastroprotective branch of the brain‐gut interactions in stress.Support or Funding InformationThe study was supported by the Russian Scientific Foundation (RSF) No 14‐15‐00790.