Rationale The most simple and efficient method to study the physiological role of enkephalins is to increase the lifetime of these entodogenous opioid peptides by inhibiting their inactivating enzymes. Enkephalins are degraded by the concomitant action of two metallopeptidases: neutral entodopeptidase (NEP, EC220.127.116.11) and aminopeptidase N (APN, EC18.104.22.168), both enzymes releasing inactive metabolites. Objectives Potent dual inhibitors have been developed, such as RB101. However, NEP and APN have a broad specificity and can cleave various peptides in vitro.
Therefore, it was essential to investigate the specific involvement of enkephalins in the various pharmacological responses induced by dual inhibitors.Download full version