title: Hemokinin-1(4-11)-induced analgesia selectively up-regulates δ-opioid receptor expression in mice.
abstract: Our previous studies have shown that an active fragment of human tachykinins (hHK-1(4-11)) produced an opioid-independent analgesia after intracerebroventricular (i.c.v.) injection in mice, which has been markedly enhanced by a δ OR antagonist, naltrindole hydrochloride (NTI). In this study, we have further characterized the in vivo analgesia after i.c.v. injection of hHK-1(4-11) in mouse model. Our qRT-PCR results showed that the mRNA levels of several ligands and receptors (e.g. PPT-A, PPT-C, KOR, PDYN and PENK) have not changed significantly. Furthermore, neither transcription nor expression of NK1 receptor, MOR and POMC have changed noticeably. In contrast, both mRNA and protein levels of DOR have been up-regulated significantly, indicating that the enhanced expression of δ opioid receptor negatively modulates the analgesia induced by i.c.v. injection of hHK-1(4-11). Additionally, the combinatorial data from our previous and present experiments strongly suggest that the discriminable distribution sites in the central nervous system between hHK-1(4-11) and r/mHK-1 may be attributed to their discriminable analgesic effects. Altogether, our findings will not only contribute to the understanding of the complicated mechanisms regarding the nociceptive modulation of hemokinin-1 as well as its active fragments at supraspinal level, but may also lead to novel pharmacological interventions.
authors.affiliation: Lab of Proteomics and Molecular Enzymology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China ; Institute for Cell-Based Drug Development of Zhejiang Province, Hangzhou, China.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Fu
authors.affiliation: Lab of Proteomics and Molecular Enzymology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Rui-Long
authors.initials: RL
authors.lastname: Xia
authors.affiliation: Lab of Proteomics and Molecular Enzymology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Zhang
authors.affiliation: Lab of Proteomics and Molecular Enzymology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Lab of Proteomics and Molecular Enzymology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Shi-Fu
authors.initials: SF
authors.lastname: Zhang
authors.affiliation: Center for BioEnergetics, The Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yu
authors.affiliation: Zhejiang Provincial People's Hospital, Hangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.affiliation: Zhejiang Provincial People's Hospital, Hangzhou, China ; Institute for Cell-Based Drug Development of Zhejiang Province, Hangzhou, China.
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Mou
mesh_terms: D000698:Analgesia; D000818:Animals; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000235:genetics* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015320:Tachykinins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D010446:Peptide Fragments; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D015320:Tachykinins; C507968:hemokinin-1; C044206:preprotachykinin; D011333:Pro-Opiomelanocortin