Protective effect of eurystatins A and B, new prolyl endopeptidase inhibitors, on scopolamine-induced amnesia in rats.
Eurystatins A and B, which are produced by Streptomyces eurythermus R353-21, potently inhibited Flavobacterium prolyl endopeptidase (PED) with IC50 values of 0.004 and 0.002 micrograms/ml, respectively, while no inhibition was observed against another 5 proteases, even at 100 micrograms/ml. The protective effect of eurystatins A and B against scopolamine (3 mg/kg, i.p.)-induced amnesia in rats was evaluated by the step-through one-trial passive avoidance method. When administered i.p. 30 min prior to the acquisition trial, both eurystatins A, at 2-8 mg/kg, and B, at 4-8 mg/kg, significantly protected rats from the amnesic effect of scopolamine without behavioral side effects.
Kamei
H
H
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Ueki
T
T
Obi
Y
Y
Fukagawa
Y
Y
Oki
T
T
D000595:Amino Acid Sequence; D000647:Amnesia / Q000139:chemically induced*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005417:Flavobacterium / Q000187:drug effects / Q000201:enzymology; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology*; D000085822:Prolyl Oligopeptidases; D051381:Rats; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D010456:Peptides, Cyclic; D015842:Serine Proteinase Inhibitors; C078927:eurystatin A; C078928:eurystatin B; D012601:Scopolamine; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases