Designing of an orally active complement C3a agonist peptide with anti-analgesic and anti-amnesic activity.
Complement C3a is an anti-opioid peptide, having anti-analgesic and anti-amnesic effects after intracerebroventricular administration. However, the peptide is inactive after oral administration. Orally active C3a agonist peptide was designed based on the structure of oryzatensin, a C3a agonist peptide derived from rice albumin. Tyr-Pro-Leu-Pro-Arg, a pentapeptide at the carboxyl terminus of oryzatensin is the minimally essential structure for exerting C3a activity. Due to the affinity for mu-opioid receptor, both oryzatensin and Tyr-Pro-Leu-Pro-Arg showed analgesia after intracerebroventricular administration in mice which was blocked by the opioid antagonist naloxone. Tyr-Pro-Leu-Pro-Arg lost opioid activity by substitution the amino terminus tyrosine with other hydrophobic residues. Among the newly designed peptides, Trp-Pro-Leu-Pro-Arg was found to possess the strongest C3a activity. The peptide antagonized morphine-induced analgesia at 300 mg/kg after oral administration and also improved scopolamine- and ischemia-induced amnesia in a step-through passive avoidance test.
Jinsmaa
Y
Y
Research Institute for Food Science, Kyoto University, Uji, 611-0011, Kyoto, Japan.
Takenaka
Y
Y
Yoshikawa
M
M
D000284:Administration, Oral; D000647:Amnesia / Q000188:drug therapy*; D000698:Analgesia; D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D003176:Complement C3 / Q000819:agonists*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
D000700:Analgesics; D003176:Complement C3; D010455:Peptides