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.
KeywordsFiltration Prostaglandin Ibuprofen Inositol Prostacyclin
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- 1.Badr KF, Brenner BM, Ichikawa II (1987) Effects of leukotriene D4 on glomerular dynamics in the rat. Am J Physiol 22: F239 - F243Google Scholar
- 4.Badr KF, Mong S, Hoover RL, Schwarzberg M, Ebert J, Jacobson HR, Harris RC (1989) Leukotriene D4 binding and signal transduction in rat glomerular mesangial cells. Am J Physiol 26: F280 - F287Google Scholar
- 6.Nicolaou KC, Marron BE, Veale CA, Webber SE, Dahlen SE, Samuelsson B, Serhan CN (1989) Identification of a novel 7-cis-1 1-trans-lipoxin A4 generated by human neutrophils: total synthesis, spasmogenic activities and comparison with other geometric isomers of lipoxins A4 and B4. Biochem Biophys Acta 1003: 44–53PubMedCrossRefGoogle Scholar
- 7.Berridge MJ (1984) Inositol trisphosphate and diacylglycerol as second messengers. Biochem J 220:345–360Google Scholar
- 8.Dahlen SE, Frazen L, Raud J, Serhan CN, Westlung P, Wikstrom E, Bjorck T, Matsuda H, Webber SE, Veale CA, Puustinen T, Haeggstrom J, Nicolaou KC, Samuelsson B (1988) Actions of lipoxin A4 and released compounds in smooth muscle preparations and on the microcirculation in vivo. In: Wong WY-K, Serhan CN (eds) Lipoxins: Biosynthesis, Chemistry and Biological activities. Plenum, New York, pp 107–130Google Scholar