Localization of orexin-1 receptors to vagal afferent neurons in the rat and humans.
OBJECTIVE
Orexin-A and -B are brain-gut peptides that stimulate food intake via orexin-R1 and -R2 receptors. Cholecystokinin (CCK) inhibits food intake via CCK(A) receptors expressed on vagal afferent neurons. The purpose of the study was to determine whether vagal afferent neurons express OX-R1 and OX-R2 and whether orexin-A inhibits responses to CCK.


METHODS
OX-R1 and -R2 expression by rat and human nodose ganglia was examined by reverse-transcriptase polymerase chain reaction (RT-PCR). Receptor localization was determined by immunohistochemistry. Responses of rat jejunal afferent fibers were examined by electrophysiology.


RESULTS
Both rat and human nodose ganglia expressed OX-R1 as detected by RT-PCR, and humans also expressed OX-R2. The identity of the products was confirmed by sequencing. Immunohistochemistry indicated expression of OX-R1 in both species in neurons that also expressed CCK(A) and leptin receptors. In human ganglia there was also expression in glial cells that was absent in rats. Orexin-A had no effect on the resting discharge of afferent nerve fibers but inhibited responses to CCK.


CONCLUSIONS
OX-R1 and CCK(A) receptors are expressed by human and rat vagal afferent neurons. Orexin inhibits responses to CCK suggesting a role in modulation of gut to brain signaling.
Burdyga
Galina
G
Department of Physiology and School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 3BX, England, UK.
Lal
Simon
S
Spiller
David
D
Jiang
Wen
W
Thompson
David
D
Attwood
Stephen
S
Saeed
Shakeel
S
Grundy
David
D
Varro
Andrea
A
Dimaline
Rod
R
Dockray
Graham J
GJ
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007583:Jejunum / Q000294:innervation; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology; D009620:Nodose Ganglion / Q000378:metabolism; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D014018:Tissue Distribution; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism*
D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D002766:Cholecystokinin