Joseph Rudinger memorial lecture: Unexpected functions of angiotensin converting enzyme, beyond its enzymatic activity

Angiotensin converting enzyme (ACE) is a well‐known enzyme, largely studied for its action on hypertension, as it produces angiotensin II from angiotensin I. This paper describes two original behaviours of ACE. We showed that ACE could hydrolyse gastrin, a neuropeptide from the gastrointestinal tract, releasing the C‐terminal amidated dipeptide H‐Asp‐Phe‐NH 2 . This dipeptide is believed to be involved in the gastrin‐induced acid secretion in the stomach. This hypothetic mechanism of action of gastrin resulted in a strategy to rationally design gastrin receptor antagonists. Beyond, we showed that the brain renin angiotensin system (RAS) could be activated by a new characterized peptide named acein, resulting in stimulation of dopamine release within the striatum. This new and original ‘receptor‐like’ activity for brain membrane‐bound ACE is quite significant taking into account the role of dopamine in the brain, particularly in neurodegenerative diseases.