Subtypes Y1 and Y2 of the Neuropeptide Y Receptor Are Respectively Expressed in Pro-Opiomelanocortin- and Neuropeptide-Y-Containing Neurons of the Rat Hypothalamic Arcuate Nucleus

Jan 16, 1998Neuroendocrinology

Different Y1 and Y2 receptors appear in two types of nerve cells controlling appetite in the rat brain's feeding center

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Abstract

A dense cluster of neuropeptide-Y (NPY)-expressing neurons in the arcuate nucleus shows complex interactions with pro-opiomelanocortin (POMC) neurons and their receptors.

Many POMC neurons express Y1 receptor (Y1-R) mRNA and protein, while some Y1-R-positive neurons do not express POMC.
NPY-positive nerve terminals are closely associated with Y1-R-like immunoreactivity at the cell membranes of POMC neurons.
Y2 receptor (Y2-R) mRNA is present in nearly all NPY-expressing neurons and also in some NPY-negative cells.
POMC neurons may be targets for NPY, suggesting a role for NPY in feeding behavior.
The findings indicate a potential distinction between post-synaptic Y1-Rs and pre-synaptic Y2-Rs in regulating NPY release.

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The arcuate nucleus of the hypothalamus houses a number of neurochemically different cell populations. Among these, a dense cluster of small neuropeptide-Y (NPY)-expressing neurons is located in its ventromedial subdivision and a pro-opiomelanocortin (POMC)-expressing neuron population in its ventrolateral part. Furthermore, both neuropeptide Y Y1 and Y2 receptors (Y1-Rs and Y2-Rs) are expressed in the arcuate nucleus. Here we analyse the co-expression of NPY and POMC/adrenocorticotropic hormone with the Y1-R and Y2-R in arcuate neurons using immunohistochemistry and in situ hybridization. Many, but not all, POMC neurons expressed Y1-R mRNA and protein. Conversely, several Y1-R-positive, POMC-negative neurons were found. NPY-positive nerve terminals were found in close apposition to Y1-R-like immunoreactivity localized close to the dendritic and somatic cell membranes. Y2-R mRNA was found in almost all NPY mRNA-expressing neurons, but also in a group of NPY mRNA-negative cells. These results show that the POMC neurons are targets for NPY, which is presumably present in, and released from, fibres originating in the ventromedial arcuate nucleus and which may play a role in NPY-induced feeding. Release of NPY, and possible coexisting messengers, may be controlled by presynaptic Y2-R expressed in NPY neurons. Taken together, the findings support the division of Y1-Rs and Y2-Rs into post- and presynaptic receptors, respectively.

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Subtypes Y1 and Y2 of the Neuropeptide Y Receptor Are Respectively Expressed in Pro-Opiomelanocortin- and Neuropeptide-Y-Containing Neurons of the Rat Hypothalamic Arcuate Nucleus

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