AJP - Renal Physiology, Vol 244, Issue 6 706-F711, Copyright © 1983 by American Physiological Society
Presence in normal human urine of a hypotensive and platelet-activating phospholipid
M. Sanchez-Crespo, P. Inarrea, V. Alvarez, F. Alonso, J. Egido and L. Hernando
Urine from normotensive volunteers and patients with systemic lupus
erythematosus glomerulonephropathy was sequentially concentrated by
negative-pressure ultrafiltration, dialyzed against distilled water, and
extracted into the chloroform phase of a mixture of organic
solvents(chloroform:methanol:water, 1:1:0.9 vol/vol). The lipid fraction
was further purified by thin-layer chromatography on silica gel plates
using neutral, acidic, and basic mixtures of organic solvents and it was
then tested for its ability to induce the release of [3H]serotonin from
rabbit platelets. All of the samples contained a platelet-activating moiety
similar to a synthetic platelet-activating factor (PAF-acether) on the
basis of its chromatographic behavior, resistance to the pretreatment of
platelets by 10(-6) M indomethacin, and loss of activity by alkaline
methanolysis or treatment by phospholipases A2, C, and D.
Cross-densensitization experiments between synthetic PAF-acether and the
urine factor showed that both compounds act on platelets through the
activation of the same putative receptor. Further, the urine factor induced
hypotension when intra-arterially injected in normotensive rats, and this
activity was also abrogated by alkaline methanolysis. In summary, these
data provide evidence of the presence in normal human urine and, probably,
of the release by the kidney of a lipid factor with platelet-activating and
hypotensive activity whose general structure seems to be
alkyl-acyl-glyceryl-phosphorylcholine and, therefore, is similar to the
structure of the inflammatory mediator PAF-acether and the antihypertensive
polar renomedullary lipid.
