The Journal of Neuroscience, February 15, 2003, 23(4):1487
Orexin Neurons Express a Functional Pancreatic Polypeptide Y4
Receptor
Rebecca E.
Campbell1, 2,
M. Susan
Smith1, 2,
Summer
E.
Allen1,
Bernadette E.
Grayson1,
Jarlath M. H.
ffrench-Mullen3, and
Kevin L.
Grove1
1 Department of Neuroscience, Oregon National Primate
Research Center, Beaverton, Oregon 97006, 2 Departments of
Physiology and Pharmacology, Oregon Health and Science University,
Portland, Oregon 97209, and 3 Gene Logic Inc.,
Gaithersburg, Maryland 20878
The receptor subtypes that mediate the effects of neuropeptide Y
(NPY) on food intake have not been clearly defined. The NPY Y4 receptor
has been identified recently as a potential mediator of the regulation
of food intake. The purpose of the present study was to characterize
the central site of action of the Y4 receptor using a combination of
neuroanatomical and physiological approaches. Using
immunocytochemistry, Y4-like immunoreactivity was found to be
colocalized with orexin cell bodies in the lateral
hypothalamic area (LHA) and orexin fibers throughout the brain.
In situ hybridization confirmed the expression of Y4
mRNA in orexin neurons. To determine the functional interaction between
Y4 receptors and orexin neurons, we examined the effects of rat
pancreatic polypeptide (rPP), a Y4-selective ligand, or NPY, a
nonselective ligand, administered directly into the LHA on the
stimulation of food and water intake and c-Fos expression. Both rPP and
NPY significantly increased food and water intake when they were
administered into the LHA, although NPY was a more potent stimulator of
food intake. Furthermore, both NPY and rPP significantly stimulated
c-Fos expression in the LHA. However, whereas rPP stimulated c-Fos
expression in orexin neurons, NPY did not. Neither rPP nor NPY
stimulated c-Fos in melanin-concentrating hormone neurons, but both
activated neurons of an unknown phenotype in the LHA. These results
suggest that a functional Y4 receptor is expressed on orexin neurons
and that these neurons are activated in response to a ligand with high affinity for the Y4 receptor (rPP). Although these data suggest a role
for central Y4 receptors, the endogenous ligand for this receptor has
yet to be clearly established.
Key words:
neuropeptide Y; pancreatic polypeptide; rat; c-Fos; orexin; feeding
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341487-11$05.00/0
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