Peripheral corticotropin releasing factor (CRF) and a novel CRF1 receptor agonist, stressin1-A activate CRF1 receptor expressing cholinergic and nitrergic myenteric neurons selectively in the colon of conscious rats.
Intraperitoneal (i.p.) corticotropin releasing factor (CRF) induced a CRF(1) 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 CRF(1) receptor expression in myenteric neurons. CRF (i.p., 10 microg 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 CRF(1) agonist, stressin(1)-A (i.p., 10 microg 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 CRF(1) 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 stressin(1)-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 CRF(1) receptor.
Yuan
P-Q
PQ
CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Digestive Diseases Division, Department of Medicine and Brain Research Institute, University of California Los Angeles 90073, USA. pqyuan@mednet.ucla.edu
Million
M
M
Wu
S V
SV
Rivier
J
J
Taché
Y
Y
D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000294:innervation* / Q000473:pathology; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism* / Q000473:pathology; D026602:Nitrergic Neurons / Q000378:metabolism* / Q000473:pathology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
D010456:Peptides, Cyclic; D016760:Proto-Oncogene Proteins c-fos; D018019:Receptors, Corticotropin-Releasing Hormone; C519520:cyclo(31-34)(phenylalanyl(12)-norleucyl(21,28)-glutamyl(31)-lysyl(34))acetyl-corticotropin releasing factor (4-41); D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone