Distribution of Y-Receptors in Murine Lingual Epithelia

Maria D Hurtado,Sergei Zolotukhin,Kirill Ukhanov,Andres Acosta,Herbert Herzog,Paola P Riveros,Cedrick D Dotson,Alicia R Brown,Bruce J Baum,Wolfgang Meyerhof

doi:10.1371/journal.pone.0046358

Abstract

Peptide hormones and their cognate receptors belonging to neuropeptide Y (NPY) family mediate diverse biological functions in a number of tissues. Recently, we discovered the presence of the gut satiation peptide YY (PYY) in saliva of mice and humans and defined its role in the regulation of food intake and body weight maintenance. Here we report the systematic analysis of expression patterns of all NPY receptors (Rs), Y1R, Y2R, Y4R, and Y5R in lingual epithelia in mice. Using four independent assays, immunohistochemistry, in situ hybridization, immunocytochemistry and RT PCR, we show that the morphologically different layers of the keratinized stratified epithelium of the dorsal layer of the tongue express Y receptors in a very distinctive yet overlapping pattern. In particular, the monolayer of basal progenitor cells expresses both Y1 and Y2 receptors. Y1Rs are present in the parabasal prickle cell layer and the granular layer, while differentiated keratinocytes display abundant Y5Rs. Y4Rs are expressed substantially in the neuronal fibers innervating the lamina propria and mechanoreceptors. Basal epithelial cells positive for Y2Rs respond robustly to PYY3–36 by increasing intracellular Ca2+ suggesting their possible functional interaction with salivary PYY. In taste buds of the circumvallate papillae, some taste receptor cells (TRCs) express YRs localized primarily at the apical domain, indicative of their potential role in taste perception. Some of the YR-positive TRCs are co-localized with neuronal cell adhesion molecule (NCAM), suggesting that these TRCs may have synaptic contacts with nerve terminals. In summary, we show that all YRs are abundantly expressed in multiple lingual cell types, including epithelial progenitors, keratinocytes, neuronal dendrites and TRCs. These results suggest that these receptors may be involved in the mediation of a wide variety of functions, including proliferation, differentiation, motility, taste perception and satiation.

Highlights

Neuropeptide Y (NPY), Peptide YY (PYY), and Pancreatic Polypeptide (PP) belong to a family of peptides sharing similar hairpin-like PP-fold structural homology and evolutionary history [1]
The innate physiological functions of salivary PYY3–36 are yet to be fully determined, we have presented data that support a role of salivary PYY in the modulation of food intake (FI) and in the accumulation of body weight
We have demonstrated the expression of Y2Rs in basal lingual epithelial cells [2]

Summary

Introduction

Neuropeptide Y (NPY), Peptide YY (PYY), and Pancreatic Polypeptide (PP) belong to a family of peptides sharing similar hairpin-like PP-fold structural homology and evolutionary history [1]. NPY is widely expressed in the central as well as in the peripheral nervous system; PYY is released mostly by L-endocrine cells in the distal gut epithelia, while PP is produced by specialized cell in the pancreas These peptides mediate various complementary and often opposing metabolic functions such as appetite and satiation, energy intake and expenditure; cell proliferation, migration, and differentiation; neuromodulation, angiogenesis, osteogenesis, and many other biological processes. This diversity of functions is mediated through the extensive redundancy of PP-fold peptides binding to five known receptors (Rs), Npy1r, Npy2r, Npy4r, Npy5r, and Npy6r (hereafter referred to as Y1R, Y2R, Y4R, Y5R, and y6R). The pharmacological redundancy of NPY family receptors is further increased by the action of dipeptidyl-peptidase-IV (DPPIV), a serine exopeptidase that truncates NPY and PYY at their N termini producing peptides NPY3–36 and PYY3–36 and thereby changing their binding specificity

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