Enzymatic barrier protects brain capillaries from leukotriene C4

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Abstract
✓ Leukotriene C4 (LTC4) increases vascular permeability in systemic, brain tumor, and ischemic brain capillaries, but not in normal brain capillaries. This study examines whether the abundance of gamma-glutamyl transpeptidase (γ-GTP) in normal brain capillaries might act as an enzymatic barrier to vasoactive leukotrienes in the brain. Blood-brain barrier (BBB) permeability was determined by quantitative autoradiography using 14C-aminoisobutyric acid. Ischemia was produced by occluding the middle cerebral artery. Seventy-two hours after occlusion, γ-GTP activity in ischemic brain disappeared, and LTC4 (4-µg total dose), which was infused into the carotid artery ipsilateral to the occlusion, selectively increased permeability, Ki, approximately twofold within core ischemic tissue and adjacent tissue, compared to vehicle alone in seven brains (15.53 ± 6.03 vs. 7.29 ± 3.36, p < 0.05, and 8.76 ± 4.02 vs. 4.32 ± 2.65, p < 0.05, respectively). No effect on BBB was seen in nonischemic brain tissue. Twenty-four ho...