Differential tissue expression of immunoreactive dehydropeptidase I, a peptidyl leukotriene metabolizing enzyme

Abstract

We previously reported that intracarotid infusion of leukotriene C 4 (LTC 4) causes a selective increase in vascular permeability within brain tumor capillaries in expermental rat brain tumor. Normal brain capillaries are rich in γ-glutamyl transpeptidase (γ-GTP), an enzyme which converts LTC 4 to leukotriene D 4 (LTD 4), and acts as an ‘enzymatic barrier’ to the vasoactive effects of LTC 4. Metabolism of LTD 4 in brain capillaries is, however, not known. In this study, rat renal dipeptidase (dehydropeptidase-I, microsomal dipeptidase; EC 3.4.13.11), which converts LTD 4 to leukotriene E 4 (LTE 4) in kidney, was purified from rat kidney and the distribution of immunoreactive dipeptidase in multiple rat organs was determind. Immunocytochemical multi-organ analysis in the rat, which included brain, lung, heart, liver, spleen, small intestine, and testis, was performed. The antigen corresponding to renal dipeptidase was recognized in lung, liver, and testis. There was no antigen in the brain, heart, spleen, and small intestine. In order to confirm the absence of dipeptidase activity in brain capillaries, the metabolism of LTD 4 by isolated brain capillaries were examined by reversed phase high performance liquid chromatography. When LTD 4 was incubated with the isolated rat brain capillary, no measurable conversion of [ 3H] LTD 4 to LTE 4 and leukotriene F 4 (LTF 4) by brain capillaries was observed with 30 min of incubation. These findings suggest that although γ-GTP acts as an enzymatic barrier and inactivates LTC 4, brain capillaries do not have metabolic activity against LTD 4.