Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Dec;56(6):1404–1410. doi: 10.1172/JCI108221

Metabolism of prostaglandins A1 and E1 in man.

M Golub, P Zia, M Matsuno, R Horton
PMCID: PMC333118  PMID: 1202078

Abstract

To investigate the in vivo whole blood metabolic clearance rates and sites of metabolism of prostaglandins A1 and E1 in man, constant infusions of the tritiated compounds were administered to normal subjects and to patients undergoing cardiac catheterization. The whole blood metabolic clearance rate of [3H]prostaglandin A1 in eight men was 5,003 +/- 864 liters/day (SD) or 2,546 +/- 513 liters/day per m2 (SD). Nonradioactive prostaglandin A1 was similarly infused in two subjects, and the metabolic clearance rates were determined, utilizing a specific radioimmunoassay. The clearance rates with this method correlated closely with those determined by the isotope infusions. Extraction studies of prostaglandin A1 showed that pulmonary, splanchnic, renal, and extremity perfusions resulted in 8.1 +/- 4.1, 56.1 +/- 10.1, 50.3 +/- 3.4, and 34.4 +/- 5.9% (SEM) removal, respectively. With [3H]=prostaglandin E1, the whole blood metabolic clearance rate was determined from the pulmonary artery concentration in three patients and averaged 4,832 +/- 1,518 liters/day (SD) or 2,686 +/- 654 liters/day per m2 (SD). Pulmonary extraction was 67.8 +/- 6.8% (SEM) and extremity removal averaged 6.6 +/- 4.9% (SEM). These results indicate that A prostaglandins are metabolized by several organs, such as the liver and kidney, and possibly by intravascular pathways as well. In man, the E prostaglandins are primarily metabolized by the lung, but extraction is not complete and approximately one-third may escape lung metabolism. Thus, these findings suggest that both E and A prostaglandins in the venous circulation may reach the systemic circulation in man.

Full text

PDF
1409

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen N. H. Dehydration of prostaglandins: study by spectroscopic method. J Lipid Res. 1969 May;10(3):320–325. [PubMed] [Google Scholar]
  2. Anggård E., Larsson C., Samuelsson B. The distribution of 15-hydroxy prostaglandin dehydrogenase and prostaglandin-delta 13-reductase in tissues of the swine. Acta Physiol Scand. 1971 Mar;81(3):396–404. doi: 10.1111/j.1748-1716.1971.tb04914.x. [DOI] [PubMed] [Google Scholar]
  3. Attallah A. A., Payakkapan W., Lee J. B. Metabolism of prostaglandin A. I. The kidney cortex as a major site of PGA2 degradation. Life Sci. 1974 Apr 16;14(8):1521–1534. doi: 10.1016/0024-3205(74)90163-5. [DOI] [PubMed] [Google Scholar]
  4. Bradley S. E., Ingelfinger F. J., Bradley G. P., Curry J. J. THE ESTIMATION OF HEPATIC BLOOD FLOW IN MAN. J Clin Invest. 1945 Nov;24(6):890–897. doi: 10.1172/JCI101676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carlson L. A., Orö L. Effect of prostaglandin E1 on blood pressure and heart rate in the dog. Prostaglandin and related factors 48. Acta Physiol Scand. 1966 May;67(1):89–99. doi: 10.1111/j.1748-1716.1966.tb03290.x. [DOI] [PubMed] [Google Scholar]
  6. Ferreira S. H., Vane J. R. Prostaglandins: their disappearance from and release into the circulation. Nature. 1967 Dec 2;216(5118):868–873. doi: 10.1038/216868a0. [DOI] [PubMed] [Google Scholar]
  7. Golub M. S., Zia P. K., Horton R. Metabolism of prostaglandins A1 and A2 by human whole blood. Prostaglandins. 1974 Oct 10;8(1):13–20. doi: 10.1016/0090-6980(74)90032-x. [DOI] [PubMed] [Google Scholar]
  8. Hamberg M., Israelsson U., Samuelsson B. Metabolism of prostaglandin E 2 in guinea pig liver. Ann N Y Acad Sci. 1971 Apr 30;180:164–180. [PubMed] [Google Scholar]
  9. Hamberg M., Samuelsson B. On the metabolism of prostaglandins E 1 and E 2 in man. J Biol Chem. 1971 Nov 25;246(22):6713–6721. [PubMed] [Google Scholar]
  10. Horton E. W., Jones R. L. Prostaglandins A1,A2 and 19-hydroxy A1; their actions on smooth muscle and their inactivation on passage through the pulmonary and hepatic portal vascular beds. Br J Pharmacol. 1969 Nov;37(3):705–722. doi: 10.1111/j.1476-5381.1969.tb08509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Horton E. W., Main I. H., Thompson C. J. Effects of prostaglandins on the oviduct, studied in rabbits and ewes. J Physiol. 1965 Oct;180(3):514–528. doi: 10.1113/jphysiol.1965.sp007714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horton R., Tait J. F. In vivo conversion of dehydroisoandrosterone to plasma androstenedione and testosterone in man. J Clin Endocrinol Metab. 1967 Jan;27(1):79–88. doi: 10.1210/jcem-27-1-79. [DOI] [PubMed] [Google Scholar]
  13. Lee J. B., McGiff J. C., Kannegiesser H., Aykent Y. Y., Mudd J. G., Frawley T. F. Prostaglandin A1: antihypertensive and renal effects. Studies in patients with essential hypertension. Ann Intern Med. 1971 May;74(5):703–710. doi: 10.7326/0003-4819-74-5-703. [DOI] [PubMed] [Google Scholar]
  14. Lee J. B. Prostaglandins and the renal antihypertensive and natriuretic endocrine function. Recent Prog Horm Res. 1974;30(0):481–532. doi: 10.1016/b978-0-12-571130-2.50016-x. [DOI] [PubMed] [Google Scholar]
  15. McGiff J. C., Crowshaw K., Itskovitz H. D. Prostaglandins and renal function. Fed Proc. 1974 Jan;33(1):39–47. [PubMed] [Google Scholar]
  16. McGiff J. C., Terragno N. A., Strand J. C., Lee J. B., Lonigro A. J., Ng K. K. Selective passage of prostaglandins across the lung. Nature. 1969 Aug 16;223(5207):742–745. doi: 10.1038/223742b0. [DOI] [PubMed] [Google Scholar]
  17. Polet H., Levine L. Metabolism of prostaglandins E, A, and C in serum. J Biol Chem. 1975 Jan 25;250(2):351–357. [PubMed] [Google Scholar]
  18. Raz A. Interaction of prostaglandins with blood plasma proteins. Comparative binding of prostaglandins A 2 , F 2 and E 2 to human plasma proteins. Biochem J. 1972 Nov;130(2):631–636. doi: 10.1042/bj1300631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Robertson R. P. Differential in vivo pulmonary degradation of prostaglandins E1, B1, and A1. Am J Physiol. 1975 Jan;228(1):68–70. doi: 10.1152/ajplegacy.1975.228.1.68. [DOI] [PubMed] [Google Scholar]
  20. Vonkeman H., Nugteren D. H., van Dorp D. A. The action of prostaglandin 15-hydroxydehydrogenase on various prostaglandins. Biochim Biophys Acta. 1969 Dec 17;187(4):581–583. doi: 10.1016/0005-2760(69)90058-7. [DOI] [PubMed] [Google Scholar]
  21. Zia P., Golub M., Horton R. A radioimmunoassay for prostaglandin A1 in human peripheral blood. J Clin Endocrinol Metab. 1975 Aug;41(2):245–252. doi: 10.1210/jcem-41-2-245. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES