Evaluation of a novel aminopeptidase N inhibitor, in vitro, using two assay systems.
The activities of the novel aminopeptidase N inhibitor (APNI), beta-Amino-alpha-Hydroxyl-Phenyl butanic acid-Valine (AHPA-Val), were compared with APNI (amastatin). AHPA-Val and amastatin produced competitive inhibition of the hydrolysis of Tyr-Gly in the guinea-pig striatal membrane preparation, with K(i) equal to 14.06 microM and 12.48 microM respectively. Met-enkephalin-induced twitch inhibition of the guinea-pig ileum preparation was enhanced by AHPA-Val and amastatin with pA(1/2) values (the negative logarithm concentration of APNI that decreased the IC(50) of Met-enkephalin by half), of 7.08 and 7.79 respectively. These results suggest that AHPA-Val has good activity as an APNI and that these two assay systems are useful for evaluating the potency of novel APNIs.
Shang
Luqing
L
Department of Pharmacology, Wakayama Medical University, Wakayama City, Wakayama, Japan. shanglq2000@yahoo.com.cn
Maeda
Takehiko
T
Xu
Wenfang
W
Kishioka
Shiroh
S
D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D006868:Hydrolysis; D007082:Ileum / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D040681:Structural Homology, Protein
D004151:Dipeptides; D011480:Protease Inhibitors; D004744:Enkephalin, Methionine; C022013:glycyltyrosine; D018826:CD13 Antigens