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Neuropeptide Y Y1 receptor knockdown can modify glutathione peroxidase and c-AMP response element-binding protein in phenylpropanolamine-treated rats

  • Molecular Toxicology
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Abstract

It has been reported that antioxidative enzymes, neuropeptide Y (NPY), and c-AMP response element-binding protein (CREB) are involved in regulating phenylpropanolamine (PPA)-mediated appetite suppression. Here, we investigated whether Y1 receptor (Y1R) might be involved in this regulation. Rats were daily treated with PPA for 4 days. Changes in the contents of NPY, Y1R, glutathione peroxidase (GP), and CREB were assessed and compared. Results showed that Y1R, GP, and CREB increased, with a maximal increase about 100, 200, and 150 %, respectively, on Day 2. By contrast, NPY decreased with a biggest reduction about 48 % on Day 2 and the pattern of expression during PPA treatment was opposite to those of Y1R, GP, and CREB. Central knockdown (using antisense) or inhibition (using antagonist) of Y1R expression modulated the anorectic response of PPA and the reciprocal regulation between NPY and GP (or CREB), revealing an essential role of Y1R in regulating NPY, GP, and CREB. These results suggest that Y1R participates in the reciprocal regulation of NPY, GP, and CREB in the hypothalamus during PPA treatment in conscious rats. The present results may aid the therapeutic research of PPA and related antiobesity drugs.

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Acknowledgments

This study was supported by a grant from the National Science Council (NSC-101-2320-B-040-002-MY3) and a grant from the Chung Shan Medical University (CSMU 101-OM-A-133).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan, ROC

    Yih-Shou Hsieh & Pei-Ni Chen

  2. National Taichung Second Senior High School, Taichung City, 404, Taiwan, ROC

    Meng-Hsien Kuo

  3. Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan, ROC

    Dong-Yih Kuo

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  1. Yih-Shou Hsieh
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  2. Pei-Ni Chen
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Correspondence to Dong-Yih Kuo.

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Hsieh, YS., Chen, PN., Kuo, MH. et al. Neuropeptide Y Y1 receptor knockdown can modify glutathione peroxidase and c-AMP response element-binding protein in phenylpropanolamine-treated rats. Arch Toxicol 87, 469–479 (2013). https://doi.org/10.1007/s00204-012-0947-7

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