Identification of functionally important dipeptide in sequences of atypical opioid peptides

The occurrence of individual amino acids and dipeptide fragments in the sequences of 60 known atypical opioid peptides was analyzed. An expressed predominance of Tyr-Pro fragment suggested a high probability of analgesic activity for this dipeptide, and it was experimentally studied. It was shown on somatic and visceral pain sensitivity models that, on the i.p. administration of Tyr-Pro at doses of 1.0-10 mg/kg of body mass, it exhibits an analgesic activity eliminated by naloxone and naloxone methiodide. However, in tests on ileum preparations of guinea pig and mouse vas deferens in vitro, Tyr-Pro was devoid of opioid activity, which proved its indirect influence on opioid receptors.