モノアミン代謝酵素活性に及ぼすグアニジノ化合物の影響に関する研究

In the central nervous system (CNS)of mammals, monoamine oxidase (EC 1.4.3.4)(MAO), which have been divided into two functional forms (MAO-A and MAO-B), and catechol-O-methyltransferase (EC 2.1.1.6)(COMT) act as catabolic enzymes of catecholamines and serotonin regulating their concentrations. In this study, the effects of guanidino compounds (5mM) on MAO-A, MAO-B and COMT were examined to invastigate the role of guanidino compounds in CNS function. MAO-A activity was decreased by α-guanidinoglutaric acid (GGA) and guanidinoethanesulfonic acid, and increased by arginine (Arg) and N-acetylarginine at a low substrate concentration (4.33μM). MAO-B activity was decreased by creatinine (CRN), δ-guanidinovaleric acid (GVA) and methylguanidine (MGua) at a high substrate concentration (3.125mM), and decreased by CRN, GVA, MGua, Arg, guanidine, 2-guanidinoethanol, β-guanidinopropionic acid, guanidinosuccinic acid and homoarginine at a low substrate concentration (62.5μM). GVA, CRN and MGua acted as competitive inhibitors on MAO-B and their calculated Ki values were 9.47mM, 14.5mM and 29.4mM, respectively. Although the guanidino compounds tested had no effect on COMT activity at a high substrate concentration (600μM), GSA and GVA inhibited COMT activity at a low substrate concentration (75μM). These results suggest that some guanidino compounds influence catabolic enzymes of indoleamine and catecholamines to control CNS function.

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