Metabolic strategies for the degradation of the neuromodulator agmatine in mammals
2017; Elsevier BV; Volume: 81; Linguagem: Inglês
10.1016/j.metabol.2017.11.005
ISSN1532-8600
AutoresJosé J. Benı́tez, David García, Nicol Romero, Arlette González, José Martínez‐Oyanedel, Maximiliano Figueroa, Mónica Salas, Vasthi López, María de los Ángeles García, Peter R. Dodd, Gerhard Schenk, Nelson Carvajal, Elena Uribe,
Tópico(s)Cannabis and Cannabinoid Research
ResumoAgmatine (1-amino-4-guanidinobutane), a precursor for polyamine biosynthesis, has been identified as an important neuromodulator with anticonvulsant, antineurotoxic and antidepressant actions in the brain. In this context it has emerged as an important mediator of addiction/satiety pathways associated with alcohol misuse. Consequently, the regulation of the activity of key enzymes in agmatine metabolism is an attractive strategy to combat alcoholism and related addiction disorders. Agmatine results from the decarboxylation of L-arginine in a reaction catalyzed by arginine decarboxylase (ADC), and can be converted to either guanidine butyraldehyde by diamine oxidase (DAO) or putrescine and urea by the enzyme agmatinase (AGM) or the more recently identified AGM-like protein (ALP). In rat brain, agmatine, AGM and ALP are predominantly localised in areas associated with roles in appetitive and craving (drug-reinstatement) behaviors. Thus, inhibitors of AGM or ALP are promising agents for the treatment of addictions. In this review, the properties of DAO, AGM and ALP are discussed with a view to their role in the agmatine metabolism in mammals.
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