Expression of type 1 corticotropin-releasing factor receptor in the guinea pig enteric nervous system.
Reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiological recording, and intraneuronal injection of the neuronal tracer biocytin were integrated in a study of the functional expression of corticotropin-releasing factor (CRF) receptors in the guinea pig enteric nervous system. RT-PCR revealed expression of CRF1 receptor mRNA, but not CRF2, in both myenteric and submucosal plexuses. Immunoreactivity for the CRF1 receptor was distributed widely in the myenteric plexus of the stomach and small and large intestine and in the submucosal plexus of the small and large intestine. CRF1 receptor immunoreactivity was coexpressed with calbindin, choline acetyltransferase, and substance P in the myenteric plexus. In the submucosal plexus, CRF1 receptor immunoreactivity was found in neurons that expressed calbindin, substance P, choline acetyltransferase, or neuropeptide Y. Application of CRF evoked slowly activating depolarizing responses associated with elevated excitability in both myenteric and submucosal neurons. Histological analysis of biocytin-filled neurons revealed that both uniaxonal neurons with S-type electrophysiological behavior and neurons with AH-type electrophysiological behavior and Dogiel II morphology responded to CRF. The CRF-evoked depolarizing responses were suppressed by the CRF1/CRF2 receptor antagonist astressin and the selective CRF1 receptor antagonist NBI27914 and were unaffected by the selective CRF2 receptor antagonist antisauvagine-30. The findings support the hypothesis that the CRF1 receptor mediates the excitatory actions of CRF on neurons in the enteric nervous system. Actions on enteric neurons might underlie the neural mechanisms by which stress-related release of CRF in the periphery alters intestinal propulsive motor function, mucosal secretion, and barrier functions.
Liu
Sumei
S
Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210-1218, USA.
Gao
Xiang
X
Gao
Na
N
Wang
Xiyu
X
Fang
Xiucai
X
Hu
Hong-Zhen
HZ
Wang
Guo-Du
GD
Xia
Yun
Y
Wood
Jackie D
JD
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D064026:Calbindins; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000294:innervation*; D006168:Guinea Pigs; D008239:Lysine / Q000031:analogs & derivatives*; D008297:Male; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013368:Submucous Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D000099052:CRF Receptor, Type 1
C471210:2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; D000814:Aniline Compounds; D064026:Calbindins; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011743:Pyrimidines; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D064030:S100 Calcium Binding Protein G; C104416:astressin; D013373:Substance P; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D002795:Choline O-Acetyltransferase; C013411:biocytin; D008239:Lysine