Enhanced carnosine (beta-alanyl-L-histidine) breakdown and histamine metabolism following treatment with compound 48/80.

We have previously suggested that carnosine may serve as a reservoir for histidine to be used as a source of histamine in the trauma response of rats. In this study we report the effect of stimulation of histamine-forming capacity by compound 48/80 on muscle carnosinase (C'ASE) and histidine decarboxylase (HDC) activities as well as on muscle carnosine and histamine concentrations. Male rats (180 g) were injected i.p. with 5 mg/kg bw of compound 48/80 and C'ASE and HDC activities as well as carnosine, histidine and histamine concentrations were monitored over a 72 h period post-injection. This treatment resulted in an 120% increase in muscle HDC activity and an 110% increase in muscle histamine concentration at 15 min post-injection, followed by an 80% increase in muscle C'ASE activity at 1 h and a 100% reduction in muscle carnosine concentration at 24 h post-injection when compared to control animals injected with 0.9% saline. Histidine concentration was not affected by treatment. The time frame of response, a rapid increase in muscle HDC activity and in muscle histamine concentration followed by an increase in muscle C'ASE activity and a later decrease in muscle carnosine concentration, suggests that carnosine is hydrolysed to liberate histidine and that carnosine, as a reservoir for histidine, is mobilized to maintain a constant muscle concentration of histidine for histamine synthesis.