Laboratory Investigation

Kidney International (1992) 41, 1543–1548; doi:10.1038/ki.1992.224

Synthesis and metabolism of cysteinyl leukotrienes by the isolated pig kidney

Kevin P Moore, Graham W Taylor, Christopher Gove, John Wood, Kai-Chah Tan, John Eason and Roger Williams

The Institute of Liver Studies, Kings College School of Medicine and Dentistry, Denmark Hill; and Department of Clinical Pharmacology, Royal Postgraduate Medical School, Du Cane Road, London, England, United Kingdom

Correspondence: Dr K Moore, Department of Clinical Pharmacology, Royal Postgraduate Medical School, Du Cane Road, London W12 0NN, England, United Kingdom.

Received 22 November 1991; Revised 16 January 1992; Accepted 16 January 1992.

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Abstract

Synthesis and metabolism of cysteinyl leukotrienes by the isolated pig kidney. The metabolism and synthesis of cysteinyl leukotrienes by the isolated perfused pig kidney has been investigated. Kidneys were maintained for up to six hours in a recirculating perfusion system by using an oxygenated Krebs-Henseleit buffer containing albumin and the perfluorinated oxygen carrier, FC-43. Perfusion pressure was maintained at 12-13.5 kPa, with perfusion flow rates of 150-250 ml/min resulting in a urine output of between 20-180 ml/hr. Infusion of 3H-LTC4 into the renal artery resulted in rapid and complete metabolism, with the major urinary metabolites comprising LTE4, omega-hydroxy-LTE4, omega-carboxy-LTE4 and N-acetyl-omega-hydroxy-LTE4. The capacity of the isolated kidney to synthesize cysteinyl leukotrienes was monitored by measuring urinary LTE4 excretion; there was a basal urinary excretion of LTE4 (median 43 pg/min, range 8-470 pg/min). Neither lipopolysaccharide or human recombinant tumor necrosis factor alpha had any effect on basal excretion. Treatment with the calcium ionophore A23187, however, resulted in a 38.1 plusminus 9.6-fold increase in urinary LTE4 excretion. We conclude that the isolated pig kidney, in the absence of circulating cells, can synthesize cysteinyl leukotrienes in the absence of circulating cells, which can then undergo extensive oxidative metabolism.

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