Differential actions of urocortins on neurons of the myenteric division of the enteric nervous system in guinea pig distal colon.
OBJECTIVE
Urocortins (Ucns) 1, 2 and 3 are corticotropin-releasing factor (CRF)-related neuropeptides and may be involved in neural regulation of colonic motor functions. Nevertheless, details of the neural mechanism of action for Ucns have been unclear. We have, here, tested the hypothesis that Ucns act in the enteric nervous system (ENS) to influence colonic motor behaviour.


METHODS
We used intracellular recording with 'sharp' microelectrodes, followed by intraneuronal injection of biocytin, and immunohistochemical localization of CRF(1) and CRF(2) receptors in guinea pig colonic tissue.


RESULTS
Application of Ucn1 depolarized membrane potentials and elevated excitability in 58% of AH-type and 60% of S-type colonic myenteric neurons. In most of the neurons tested, depolarizing responses evoked by Ucn-1 were suppressed by the CRF(1) receptor antagonist NBI 27914, but were unaffected by the CRF(2) receptor antagonist antisauvagine-30. The selective CRF(2) receptor agonists, Ucn2 and Ucn3, evoked depolarizing responses in 12 and 8% of the AH-type myenteric neurons, respectively, and had no effect on S-type neurons. Antisauvagine-30, but not NBI 27914, suppressed these Ucn2- and Ucn3-evoked responses. Immunohistochemical staining identified CRF(1) as the predominant CRF receptor subtype expressed by ganglion cell somas, while CRF(2)-immunoreactive neuronal somas were sparse. Ucns did not affect excitatory synaptic transmission in the ENS.


CONCLUSIONS
The results suggest that Ucns act as neuromodulators to influence myenteric neuronal excitability. The excitatory action of Ucn1 in myenteric neurons was primarily at CRF(1) receptors, and the excitatory action of Ucn2 and Ucn3 was at CRF(2) receptors.
Liu
Sumei
S
Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, OH, USA. liu.sume@uwlax.edu
Ren
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MH
Bishop
G A
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Wang
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Wang
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Xia
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Wood
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D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000378:metabolism*; D017615:Enteric Nervous System / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D008839:Microelectrodes; D009197:Myenteric Plexus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism*; D054832:Urocortins / 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; C101531:CRF receptor type 2; D010446:Peptide Fragments; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C116607:antisauvagine 30; D000099052:CRF Receptor, Type 1