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Keywords:

  • colonic motility;
  • corticotropin releasing factor;
  • CRF1 receptor;
  • enteric nervous system;
  • Fos;
  • peripheral choline acetyltransferase;
  • stressin1-A

Abstract  Intraperitoneal (i.p.) corticotropin releasing factor (CRF) induced a CRF1 receptor-dependent stimulation of myenteric neurons and motility in the rat proximal colon. We characterize the colonic enteric nervous system response to CRF in conscious rats. Laser capture microdissection combined with reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry in longitudinal muscle myenteric plexus whole-mount colonic preparations revealed CRF1 receptor expression in myenteric neurons. CRF (i.p., 10 μg kg−1) induced Fos immunoreactivity (IR) (cells per ganglion) selectively in myenteric plexus of proximal (18.3 ± 2.4 vs vehicle: 0.0 ± 0.0) and distal colon (16.8 ± 1.2 vs vehicle: 0.0 ± 0.0), but not in that of gastric corpus, antrum, duodenum, jejunum and ileum. The selective CRF1 agonist, stressin1-A (i.p., 10 μg kg−1) also induced Fos IR in myenteric but not in submucosal plexus of the proximal and distal colon. Fos IR induced by CRF was located in 55 ± 1.9% and 53 ± 5.1% of CRF1 receptor-IR myenteric neurons and in 44 ± 2.8% and 40 ± 3.9% of cholinergic neurons with Dogiel type I morphology, and in 20 ± 1.6% and 80 ± 3.3% of nitrergic neurons in proximal and distal colon respectively. CRF and stressin1-A elicit defecation and diarrhoea. These data support that one mechanism through which peripherally injected CRF ligands stimulate colonic function involves a direct action on colonic cholinergic and nitrergic myenteric neurons expressing CRF1 receptor.