DIFFERENTIAL TISSUE EXPRESSION OF IMMUNOREACTIVE DEHYDROPEPTIDASE-I, A PEPTIDYL LEUKOTRIENE METABOLIZING ENZYME

We previously reported that intracarotid infusion of leukotriene C-4 ( LTC(4)) causes a selective increase in vascular permeability within br ain tumor capillaries in experimental rat brain tumor. Normal brain ca pillaries are rich in gamma-glutamyl transpeptidase (gamma-GTP), an en zyme which converts LTC(4) to leukotriene D-4 (LTD(4)), and acts as an 'enzymatic barrier' to the vasoactive effects of LTC(4). Metabolism o f LTD(4) in brain capillaries is, however, not known. In this study, r at renal dipeptidase (dehydropeptidase-I, microsomal dipeptidase; EC 3 .4.13.11), which converts LTD(4) to leukotriene E(4) (LTE(4)) in kidne y, 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, li ver, spleen, small intestine, and testis, was performed. The antigen c orresponding to renal dipeptidase was recognized in lung, liver, and t estis. There was no antigen in the brain, heart, spleen, and small int estine. In order to confirm the absence of dipeptidase activity in bra in capillaries, the metabolism of LTD, by isolated brain capillaries w ere examined by reversed phase high performance liquid chromatography. When LTD(4) was incubated with the isolated rat brain capillary, no m easurable conversion of [H-3] LTD(4) to LTE(4) and leukotriene F-4 (LT F(4)) by brain capillaries was observed with 30 min of incubation. The se findings suggest that although gamma-GTP acts as an enzymatic barri er and inactivates LTC(4), brain capillaries do not have metabolic act ivity against LTD(4).