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

5 years ago

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

Jean Martinez

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-NH2. 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. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Angiotensin converting enzyme (ACE) is well known for its enzymatic activity. Besides, it can be associated with the gastrin receptor to play a role in the mechanism of action of the hormone. Brain-bound membrane ACE can also be activated by the new characterized nonapeptide named acein to stimulate dopamine release within the striatum of rodents. Beyond its enzyme activity, does ACE act as an enzyme-associated receptor, does it exhibit a ‘receptor-like’ activity? Is the duo acein/ACE involved in neurodegenerative disorders?

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/psc.3022