Synthetic Peptide TPLVTLFK, a Selective Agonist of Nonopioid β-Endorphin Receptor, Reduces the Corticotropin and Corticosterone Response
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- 作者：Elena V. Navolotskaya…
- 关键词：Peptide ; Receptor ; Signal transduction ; Corticotrophin ; Corticosterone
- 刊名：International Journal of Peptide Research and Therapeutics
- 出版年：2017
- 出版时间：March 2017
- 年：2017
- 卷：23
- 期：1
- 页码：111-118
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biochemistry, general; Animal Anatomy / Morphology / Histology; Polymer Sciences; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Molecular Medicine;
- 出版者：Springer Netherlands
- ISSN：1573-3904
- 卷排序：23
文摘
The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12–19 of β-endorphin, a selective agonist of nonopioid β-endorphin receptor, was labeled with tritium to specific activity of 29 Ci/mmol. The analysis of the specific binding of [3H]octarphin to anterior pituitary membranes obtained from rats before and after the lipopolysaccharide (LPS)-injection showed that 2 h after LPS administration the value of maximal binding capacity of the membranes (Bmax) was increased by 1.6 times (Bmax 12.3 ± 0.8 and 20.0 ± 1.9 pmol/mg of protein, respectively), while the binding affinity was not changed (Kd 5.8 ± 0.3 and 5.5 ± 0.4 nM, respectively). At the same time, LPS did not have a significant effect on the characteristics of the labeled peptide binding to adrenal cortex membranes. Intranasal injection of octarphin at doses of 10–30 μg/rat was found to reduce the LPS-induced corticotropin and corticosterone response. The effect of the peptide was dose-dependent with a maximum at a dose 20 μg/rat. Aminoguanidine (AG 100 mg/kg i.p.), a selective inducible nitric oxide synthase (iNOS) inhibitor, completely abolished the inhibitory effect of the peptide on the LPS-induced corticotropin and corticosterone response. At the same time, octarphin in vitro stimulated in a time- and concentration-dependent manner the anterior pituitary iNOS expression of rats injected with LPS (1 mg/kg i.p.). The maximum level of the iNOS expression was observed at a peptide concentration of 10 nM after 2 h cultivation. These results indicate that the inhibitory effect of octarphin on LPS-induced secretion of corticotropin and corticosterone due to the ability of the peptide to stimulate the expression of iNOS in the anterior pituitary.