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

We previously reported that intracarotid infusion of leukotriene C4 (LTC4) causes a selective increase in vascular permeability within brain tumor capillaries in experimental rat brain tumor. Normal brain capillaries are rich in gamma-glutamyl transpeptidase (gamma-GTP), an enzyme which converts LTC4 to leukotriene D4 (LTD4), and acts as an 'enzymatic barrier' to the vasoactive effects of LTC4. Metabolism of LTD4 in brain capillaries is, however, not known. In this study, rat renal dipeptidase (dehydropeptidase-I, microsomal dipeptidase; EC 3.4.13.11), which converts LTD4 to leukotriene E4 (LTE4) in kidney, was purified from rat kidney and the distribution of immunoreactive dipeptidase in multiple rat organs was determined. 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 LTD4 by isolated brain capillaries were examined by reversed phase high performance liquid chromatography. When LTD4 was incubated with the isolated rat brain capillary, no measurable conversion of [3H] LTD4 to LTE4 and leukotriene F4 (LTF4) by brain capillaries was observed with 30 min of incubation. These findings suggest that although gamma-GTP acts as an enzymatic barrier and inactivates LTC4, brain capillaries do not have metabolic activity against LTD4.