Neuropeptide Y Y1 receptor knockdown can modify glutathione peroxidase and c-AMP response element-binding protein in phenylpropanolamine-treated rats.
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.
Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan, ROC.
Yih-Shou
YS
Hsieh
Pei-Ni
PN
Chen
Meng-Hsien
MH
Kuo
Dong-Yih
DY
Kuo
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001069:Appetite Regulation / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004435:Eating / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D010665:Phenylpropanolamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D001067:Appetite Depressants; C092926:BIBP 3226; C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D009478:Neuropeptide Y; C066211:Npy1r protein, rat; D016376:Oligonucleotides, Antisense; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D010665:Phenylpropanolamine; D001120:Arginine; D005979:Glutathione Peroxidase