Plasma Agmatine and Platelet Imidazoline Receptors in Depression^a

Abstract

Plasma agmatine concentrations are elevated significantly in depressed patients compared to healthy controls. Treatment with the antidepressant bupropion normalized plasma agmatine levels. Correlational evidence is presented that a change in plasma agmatine levels may lead to similar changes in platelet I1 imidazoline receptors.

Regulatory mechanisms underlying agmatine homeostasis in humans

“…Since, in fact, blood samples were always taken from the portal and hepatic veins at the same time, possible periodic changes in absorption cannot account for differences of agmatine levels between the corresponding blood samples. In the blood of all patients, agmatine could be detected at concentrations similar to those previously reported for humans (5,28). The agmatine levels found in the patients were also comparable to those in rat blood determined in our laboratory with the same methods (means Ϯ SE: 0.97 Ϯ 0.23 ng/ml plasma; n ϭ 38).…”

Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats

“…Terapijski potencijal AGM kao suplementa ukoliko se primenjuje 4-6 nedelja svakodnevno potvrđen je kod odraslih pacova kako na bihejvioralnom, tako i na neurohemijskom nivou (10). Dokazana je i povećana koncentracija AGM u plazmi kod nekih psihijatrijskih oboljenja (shizofrenija i depresija) (11,12). Istraživanja na životinjama pokazuju da AGM aplikovan intraćelijski ili sistemski smanjuje propadanje neurona u patološkim stanjima, na primer, ishemiji (13) ili delovanju toksina (14).…”

“…Sa druge strane, terapijski potencijal AGM kao suplementa potvrđen je kod odraslih pacova na bihejvioralnom (poboljšava prostorno učenje u vodenom lavirintu) i neurohemijskom nivou (smanjuje aktivnost azot oksid sintaze) (10). Iako je poznat više od 100 godina, zbog mnogo kontroverzi, biosinteza AGM je kod ljudi nedovoljno poznata (12), uključujući i njegov uticaj na toksikokinetiku HPZ. Naši preliminarni rezultati na osnovu primenjene samo po jedne doze HPZ i AGM na ovom eksperimentalnom modelu ukazuju na potencijalno protektivno dejstvo AGM, koji pokazuje sposobnost da koriguje promene pokazatelja oksidativnog stresa izazvane HPZ i predstavljaju dokaz njegovog potencijalnog značaja u kombinovanom terapijskom pristupu u tretmanu toksičnih efekata ovog antipsihotika.…”

Agmatine Enhances the NADPH Oxidase Activity of Neuronal NO Synthase and Leads to Oxidative Inactivation of the Enzyme

“…Agmatine is produced in the brain and stored in neurons (Sastre et al, 1997;Reis and Regunathan, 1999), and it would likely interact with nNOS. The levels of agmatine are known to be elevated in depression (Halaris et al, 1999) and modulated by lipopolysaccharides and cytokines (Sastre et al, 1998). Thus, our findings on nNOS inactivation and activation of the NADPH oxidase activity has potential physiological or pathological consequences due to changes in the balance between reactive oxygen species and NO production.…”