Abstract
Previous study demonstrated that an increment of glomerular eicosanoid production may contribute to the haemodynamic changes in the obstructed kidney. To elucidate the mechanisms responsible for enhanced glomerular eicosanoid production, the present study was designed to investigate activities of related enzymes by isolated glomeruli from rat kidney with unilateral ureteral obstruction (UUO) or bilateral ureteral obstruction (BUO) for 24 hours. The activity of phospholipase A2 (PLA2) was determined by monitoring [14C] arachidonate release using [14C] phosphatidylcholine (PC) or [14C] phosphatidylethanolamine (PE) as a substrate. Phospholipase C (PLC) activity was assayed by measuring the release of [3H] inositol triphosphate ([3H] IP3) from [3H] phosphatidylinositol 4,5-biphosphate ([3H] IP2). The activity of PE-specific PLA2 was increased in glomeruli from the kidney with BUO and the contralateral kidney of unilateral ureteral obstruction (CLK). PLC activity was significantly greater in the cytosolic fraction of glomeruli from kidneys with UUO, BUO and CLK compared to sham-operated control. The activity of PC-specific PLA2 was not significantly increased in any group. These results indicate that the increased synthesis of eicosanoids by glomeruli from obstructed kidney may be mediated by enhanced activities of PE-specific PLA2 and PLC. The increased activities of these phospholipases by glomeruli from CLK may contribute to a compensatory response.
Similar content being viewed by others
References
Klahr, S., Harris, K. P. G., Purkerson, M. L.: Effects of obstruction on renal function.Pediatr. Nephrol., 2, 34 (1988).
Klahr, S.: New insight into the consequences and mechanisms of renal impairment in obstructive nephropathy.Am. J. Kidney Dis., 18, 689 (1991).
Yarger, W. E., Shocken, D. D., Harris, R. H.: Obstructive nephropathy in the rat: Possible roles for the renin-angiotensin system, prostaglandins and thromboxanes in postobstructive renal function.J. Clin. Invest., 65, 400 (1980).
Reyes, A. A., Klahr, S.: Renal function after release of ureteral obstruction: Role of endothelin and the renal artery endothelium.Kidney Int., 42, 632 (1992).
Morrison, A. R., Nishikawa, K., Needleman, P.: Thromboxane A2 biosynthesis in the ureter obstructed isolated perfused kidney of the rabbit.J. Pharmacol. Exp. Ther., 105, 1 (1978).
Nishikawa, K., Morrison, A. R., Needleman, P.: Exaggerated prostaglandin biosynthesis and its influence on renal resistance in the isolated hydronephrotic rabbit kidney.J. Clin. Invest., 59, 1143 (1977).
Yanagisawa, H., Morrissey, J., Morrison, A. R., Klahr, S.: Eicosanoid production by isolated glomeruli of rats with unilateral ureteral obstruction.Kidney Int., 37, 1528 (1990).
Schreiner, G. F., Harris, K. P. G., Purkerson, M. L., Klahr, S.: Immunological aspects of acute ureteral obstruction: Immune cell infiltrate in the kidney.Kidney Int., 34, 487 (1988).
Harris, K. P. G., Schreiner, G. P., Klahr, S.: Effect of leukocyte depletion on the function of the postobstructed kidney in the rat.Kidney Int., 36, 210 (1989).
Fukuzaki, A., Morrissey, J., Klahr, S.: Role of glomerular eicosanoid production in the obstructed kidney.Int. Urol. Nephrol., 25, 525 (1993).
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent.J. Biol. Chem., 193, 265 (1951).
Craven, P. A., Patterson, M. C., DeRubertis, F. R.: Role of enhanced arachidonate availability through phospholipase A2 pathway in mediation of increased prostaglandin synthesis by glomeruli from diabetic rats.Diabetes, 37, 429 (1988)
Felder, C. C., Jose, P. A., Axelrod, J.: The dopamine-1 agonist, SKF 82526, stimulates phospholipase C activity independent of adenylate cyclase.J. Pharmacol. Exp. Ther., 248, 171 (1989).
Yanagisawa, H., Morrissey, J., Klahr, S.: Mechanism of enhanced eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction.Am. J. Physiol., 261, F248 (1991).
Yanagisawa, H., Morrissey, J., Yates, J., Hayes, C., Klahr, S.: Protein increases glomerular eicosanoid production and activity of related enzymes.Kidney Int., 41, 1000 (1992).
Flower, R. G., Blackwell, G. L.: The importance of phospholipase A2 in prostaglandin synthesis.Biochem. Pharmacol., 25, 285 (1976).
Bonventre, J. V., Nemenoff, R.: Renal tubular arachidonic acid metabolism.Kidney Int., 39, 438 (1991).
Benabe, J. E., Spry, L., Morrison, A. R.: Effects of A II on phosphatidylinositol and polyphosphoinositide turnover in rat kidney: Mechanism of prostaglandin release.J. Biol. Chem., 257, 7430 (1982).
Schlondorff, D., Ardaillou, R.: Prostaglandins and other arachidonic acid metabolites in the kidney.Kidney Int., 29, 108 (1986).
Yanagisawa, H., Morrissey, J., Morrison, A. R., Purkerson, M. L., Klahr, S.: Role of ANG II in eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction.Am. J. Physiol., 258, F85 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fukuzaki, A., Morrissey, J. & Klahr, S. Enhanced glomerular phospholipase activity in the obstructed kidney. International Urology and Nephrology 27, 783–790 (1995). https://doi.org/10.1007/BF02552148
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02552148