The Functional Significance of Lipoxygenase Products of Arachidonic Acid in the Glomerular Microcirculation
Intrarenal administration of Lipoxin A4 (LXA4) results in vasodilatory responses, but reduces the ultrafiltration coefficient, Kf. Lipoxin A4 competes for the 3H-Leukotriene D4 (LTD4) binding to rat mesangial cells and stimulates inositol trisphosphate (INsP3) formation from these cells. Reversal of stereochemical orientation of the polar substituents at C5 and C6 from S,R to R,S in both LTD4 and LXA4 abolishes both homologous and heterologous competition for 3H-LTD4 binding to mesangial cells and leads to total loss of biologic activity. Taken together, these data provided evidence for the involvement of a common recognition site mediating the actions of these two eicosanoids on mesangial cells. Cyclooxygenase inhibition reversed the vasodilatory action of LXA4, suggesting that LXA4-mediated increases in RPF were due to the secondary release of vasodilatory cyclooxygenase products. Intrarenal arterial administration of other lipoxins, LXB4 and 7-cis, 11-trans LXA4, induced vasoconstriction. Administration of the last named lipoxin which has a configuration at C5 and C6 identical with that of LTD4, resulted in systemic and renal effects similar to those of LTD4, suggesting that these actions resulted from activation of LTD4 receptor-coupled responses.
KeywordsMesangial Cell Left Renal Artery Inositol Trisphosphate Lipoxygenase Product Intrarenal Arterial Administration
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