Evaluation of a novel aminopeptidase N inhibitor, in vitro, using two assay systems

Abstract

The activities of the novel aminopeptidase N inhibitor (APNI), β-Amino-α-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 μM and 12.48 μM 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 IC₅₀ 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.

Keywords::

• Aminopeptidase N
• AHPA-Val
• Met-enkephalin
• pA_1/2 value
• inhibition

Acknowledgements

This study was supported by a Medical research grant from Wakayama Foundation for the Promotion of Medicine. The authors thank Dr. James H. Woods and Dr. Gail Winger (Department of Pharmacology, the University of Michigan) for their advice concerning this manuscript.