Corticotropin-releasing factor type 1 receptors in the rat nodose ganglion are involved in the transduction of stress-induced visceral sensory signals to the brain

Corticotropin-releasing factor (CRF) plays roles in stress-related responses through its type 1 (CRF₁) and type 2 receptors. Both CRF and CRF₁ are expressed in the rat colon. Peripheral CRF administration and various stressors increase colonic motility and defecation. Stress induces CRF release in the colon, suggesting CRF may mediate stress-related responses of the colon. The vagal nodose ganglion (NG) transduces visceral information, including colonic sensation, to the brain. However, it remains unclear whether the CRF/CRF₁ system is involved in vagal afferent functions. This study, therefore, aimed to clarify the involvement of the CRF/CRF₁ system in relaying visceral sensory information to the brain and the effect of stress exposure on vagal nerve function. The experiments were conducted in male rats. First, CRF₁-like immunoreactivity (CRF₁-LI) was characterized in the NG. Second, the effects of vagotomy on CRF₁-LI in the NG, intraperitoneally administered CRF-induced fecal output, and c-Fos expression in the nucleus tractus solitarius (NTS) were evaluated. Subsequently, a fast blue retrograde tracer was microinjected into the proximal colon. Finally, we analyzed CRF- or stress-induced phosphorylation of cyclic AMP-response element-binding protein (pCREB) in the NG. CRF₁ mRNA and CRF₁-LI were detected, and CRF₁-LI accumulated on the proximal side of the ligated region of the nerve trunk, and CRF₁-LI was detected in most cholinergic neurons. CRF₁ siRNA suppressed the expression of CRF₁-LI in the NG. Subdiaphragmatic vagotomy decreased the number of CRF₁-positive cells in the NG while it did not affect CRF-induced fecal output. CRF-induced c-Fos expression in the NTS was suppressed by vagotomy. A neuronal tracing study showed that approximately half of CRF₁-positive cells expressed fast blue in the NG. Intraperitoneal CRF, a selective CRF₁ agonist, or immobilization stress induced pCREB expression and increases in CRF₁-positive cells in the NG. In contrast, a CRF₁ antagonist reduced the immobilization-induced increase in the expression of pCREB in the NG. These results suggest that the CRF/CRF₁ system is involved in the signal transduction of colonic sensory information to the central nervous system via the NG.

corticotropin‐releasing factor type 1 receptor; immunoreactivity; nodose ganglion; stresscolon.