Abstract :Abstract
Lactomedin-2 (LM-2: CFQWQR), isolated from a trypsin digest of human lactoferrin as an ileum-contracting peptide, exhibited a weak affinity (Ki=62 mM) 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.