Inhibition of GTP cyclohydrolase enhances intestinal inflammation in mice

Background and aims: GTP cyclohydrolase (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis which is an essential cofactor for catecholamine, serotonin and nitric oxide production. GCH1 is a key modulator of peripheral neuropathic and inflammatory pain. However, the role of GCH1 in the intestinal inflammation is not well understood. Methods and results: We studied the role of GCH1 by using the GCH1 inhibitor, diaminohydropyrimidine (DAHP) in a mouse model of dextran sodium sulphate induced colitis. Mice were challenged with 2.5% DSS for 10 days to induce colitis and were treated with DAHP…