Ann Pharmacol Pharm | Volume 2, Issue 10 | Research Article | Open Access
Masaaki Yoshikawa1,2,*, Akihiro Yoshikawa1 and Soushi Sonoda2
1Functional Research Laboratory, Japan
2Research Institute for Production Development, Japan
*Correspondance to: Masaaki Yoshikawa
Fulltext PDFLactomedin-2 (LM-2: CFQWQR), isolated from a trypsin digest of human lactoferrin as an ileumcontracting peptide, exhibited a weak affinity (Ki=62 μM) for the human oxytocin receptor (OT-R). LM-2 also exerted an anxiolytic-like activity in male mice at doses of 0.1 nmol/mouse (icv), 0.3 to 1 mg/kg (ip) and 30 mg/kg (po), as evaluated by the elevated plus-maze test. Furthermore, LM-2 exerted anxiolytic-like activity at a dose of 1.0 mg/kg when orally administered as an emulsion in 30% egg yolk. The anxiolytic-like activity of LM-2 after icv administration was blocked by L-371257, an antagonist of the OT-R. LM-2 was thus demonstrated to be an agonist peptide of the OT-R, the first to be derived from a natural protein other than preproxytocin. It is also the first example of an orally effective OT-R agonist peptide. The anxiolytic-like activities of LM-2 were blocked by SCH58267, an antagonist of the adenosine A2A receptor. It was also shown the first time that the anxiolytic-like activity of oxytocin was blocked by SCH58267. Furthermore, the anxiolytic activity of LM-2, as well as that of oxytocin, was blocked by bicuculine, an antagonist of the GABAA receptor. From these results it is concluded that the anxiolytic-like activities of LM-2 and oxytocin are mediated successively by the adenosine-A2A receptor and GABA-GABAA receptor systems downstream of the OT-R.
Yoshikawa M, Yoshikawa A, Sonoda S. Anxiolytic-Like Activity and Mode of Action of Lactomedin-2, an Oxytocin Receptor Agonist Peptide Derived from Human Lactoferrin. Ann Pharmacol Pharm. 2017; 2(10): 1098.