Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system

J Comp Neurol. 2006 Jan 1;494(1):63-74. doi: 10.1002/cne.20781.


Immunofluorescence was used to study immunoreactivity (IR) for corticotropin-releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was expressed in both the myenteric and the submucosal plexuses of all regions of the large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve fibers were present in the myenteric and submucosal plexuses, in the circular muscle coat, and surrounding submucosal arterioles. Most of the CRF-IR fibers persisted in the myenteric and submucosal plexuses after 7 days in organotypic culture. CRF-IR was not coexpressed with tyrosine hydroxylase-IR or calcitonin gene-related peptide-IR fibers. The proportions of CRF-IR cell bodies in the myenteric plexus increased progressively from the stomach (0.6%) to the distal colon (2.8%). Most of the CRF-IR myenteric neurons (95%) had uniaxonal morphology; the remainder had Dogiel type II multipolar morphology. CRF-IR cell bodies in the myenteric plexus of the ileum expressed IR for choline acetyltransferase (56.9%), substance P (55.0%), and nitric oxide synthase (37.9%). CRF-IR never colocalized with IR for calbindin, calretinin, neuropeptide Y, serotonin, or somatostatin in the myenteric plexus. CRF-IR cell bodies were more abundant in the submucosal plexus (29.9-38.0%) than in the myenteric plexus. All CRF-IR neurons in submucosal ganglia expressed vasoactive intestinal peptide-IR and were likely to be secretomotor/vasodilator neurons. CRF-IR neurons did not express IR for the CRF(1) receptor. CRF(1)-IR was expressed in neuronal neighbors of those with CRF-IR. Collective evidence suggests that VIPergic secretomotor neurons might provide synaptic input to neighboring cholinergic neurons.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindin 2
  • Calbindins
  • Calcitonin Gene-Related Peptide / metabolism
  • Cell Count / methods
  • Choline O-Acetyltransferase / metabolism
  • Colchicine / pharmacology
  • Corticotropin-Releasing Hormone / metabolism*
  • ELAV Proteins / metabolism
  • Enteric Nervous System / cytology*
  • Guinea Pigs
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Male
  • Myenteric Plexus / cytology
  • Myenteric Plexus / drug effects
  • Myenteric Plexus / metabolism
  • Neurons / chemistry
  • Neurons / metabolism*
  • Neuropeptide Y / metabolism
  • Nitric Oxide Synthase / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • Pyloric Antrum / cytology
  • Pyloric Antrum / drug effects
  • Pyloric Antrum / metabolism
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • S100 Calcium Binding Protein G / metabolism
  • Serotonin / metabolism
  • Somatostatin / metabolism
  • Substance P / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • Urocortins
  • Vasoactive Intestinal Peptide / metabolism


  • Calbindin 2
  • Calbindins
  • ELAV Proteins
  • Neuropeptide Y
  • Receptors, Corticotropin-Releasing Hormone
  • S100 Calcium Binding Protein G
  • Urocortins
  • Serotonin
  • Substance P
  • Vasoactive Intestinal Peptide
  • Somatostatin
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone
  • Nitric Oxide Synthase
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase
  • Phosphopyruvate Hydratase
  • Calcitonin Gene-Related Peptide
  • Colchicine