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. 1969 Oct;204(3):653–668. doi: 10.1113/jphysiol.1969.sp008937

The clearance and antidiuretic potency of neurohypophysial hormones in man, and their plasma binding and stability

Miriam Fabian, Mary L Forsling, J J Jones, J S Pryor
PMCID: PMC1351579  PMID: 5824107

Abstract

1. Bio-assay techniques have been used to measure plasma levels of neurohypophysial hormones in man, following either a single injection or a continuous infusion.

2. The median half-life of oxytocin after a single injection of 2 u. was 3·2 min (2·0-5·7, 95% confidence limits); this increased significantly (P < 0·01) to 4·8 min (4·4-6·1) when the hormone was infused at a rate of 500 m-u./min. The vasopressins had appreciably longer half-lives. After a single injection of 1 or 1·5 u. 8-lysine vasopressin (LVP), the half-life was 5·7 min (3·6-6·0). Continuous infusions of the hormones at a rate of 120 m-u./min yielded half-lives of 5·5 min (5·0-7·1) for LVP, and 5·6 min (3·9-9·5) for 8-arginine vasopressin (AVP).

3. The apparent volumes of distribution of the hormones were all of the order of two thirds the extracellular volume.

4. In accordance with its shorter half-life, the clearance of oxytocin was greater than that of the vasopressins (1·5 l./min, compared with 1·0 l./min).

5. The antidiuretic potencies of the hormones were studied in over-hydrated subjects, by measuring the rate of urine excretion following an I.V. injection. Duration of antidiuretic action increased in the order: oxytocin, LVP, AVP. A 5:1 mixture of oxytocin and AVP was not as long-lasting as AVP alone. 8·5% (4-22) of an administered dose of AVP was excreted in the urine, and this amount was significantly correlated with urine volume (r = +0·67, P < 0·05).

6. Ultrafiltration of human plasma containing exogenous hormones showed that 30% (13-50) of AVP was bound, the degree of binding being independent of concentration over the range used (50-400 μ-u./ml.) In contrast, oxytocin was completely unbound.

7. Exogenous oxytocin was more stable than exogenous AVP in human plasma. At 4° C there was no significant loss of oxytocin until 7 days, whereas 20% of AVP was inactivated in 2 days. At 37° C a 20% loss of AVP occurred within 4 hr, and a 50% loss within 24 hr; corresponding times for oxytocin were 24 and 48 hr.

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Selected References

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

  1. Ahmed A. B., George B. C., Gonzalez-Auvert C., Dingman J. F. Increased plasma arginine vasopressin in clinical adrenocortical insufficeincy and its inhibition by glucosteroids. J Clin Invest. 1967 Jan;46(1):111–123. doi: 10.1172/JCI105504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BURN G. P., GREWAL R. S. The antidiuretic response to and excretion of pituitary (posterior lobe) extract in man, with reference to the action of nicotine. Br J Pharmacol Chemother. 1951 Sep;6(3):471–482. doi: 10.1111/j.1476-5381.1951.tb00658.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bisset G. W., Clark B. J., Haldar J., Harris M. C., Lewis G. P., Rocha e Silva R., Jr The assay of milk-ejecting activity in the lactating rat. Br J Pharmacol Chemother. 1967 Nov;31(3):537–549. doi: 10.1111/j.1476-5381.1967.tb00418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brook A. H., Share L. On the question of protein binding and the diffusibility of circulating antidiuretic hormone in the dog. Endocrinology. 1966 Apr;78(4):779–785. doi: 10.1210/endo-78-4-779. [DOI] [PubMed] [Google Scholar]
  5. CZACZKES J. W., KLEEMAN C. R., KOENIG M. PHYSIOLOGIC STUDIES OF ANTIDIURETIC HORMONE BY ITS DIRECT MEASUREMENT IN HUMAN PLASMA. J Clin Invest. 1964 Aug;43:1625–1640. doi: 10.1172/JCI105038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DICKER S. E. A method for the assay of very small amounts of antidiuretic activity with a note on the antidiuretic titre of rat's blood. J Physiol. 1953 Oct;122(1):149–157. doi: 10.1113/jphysiol.1953.sp004986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DIECKMANN W. J., EGENOLF G. F., MORLEY B., POTTINGER R. E. The inactivation of the antidiuretic hormone of the posterior pituitary gland by blood from pregnant patients. Am J Obstet Gynecol. 1950 Nov;60(5):1043–1050. doi: 10.1016/0002-9378(50)90509-6. [DOI] [PubMed] [Google Scholar]
  8. FREY J., KERP L., REICHARDT W. Zum Vasopressin-Oxytocin-Antagonismus beim Menschen. Klin Wochenschr. 1959 Apr 1;37(7):325–329. doi: 10.1007/BF01483481. [DOI] [PubMed] [Google Scholar]
  9. Fabian M., Forsling M. L., Jones J. J., Lee J. The release, clearance and plasma protein binding of oxytocin in the anaesthetized rat. J Endocrinol. 1969 Feb;43(2):175–189. doi: 10.1677/joe.0.0430175. [DOI] [PubMed] [Google Scholar]
  10. Forsling M. L., Jones J. J., Lee J. Factors influencing the sensitivity of the rat to vasopressin. J Physiol. 1968 May;196(2):495–505. doi: 10.1113/jphysiol.1968.sp008520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GUHL U. [Antidiuretic and pressor effects of arginine-8-vasopressin, lysine-8-vasopressin, phenylalanine-2-lysine-8-vasopressin in man]. Schweiz Med Wochenschr. 1961 Jul 8;91:798–804. [PubMed] [Google Scholar]
  12. HOLLIDAY M. A., BURSTIN C., HARRAH J. EVIDENCE THAT THE ANTIDIURETIC SUBSTANCE IN THE PLASMA OF CHILDREN WITH NEPHROGENIC DIABETES INSIPIDUS IS ANTIDIURETIC HORMONE. Pediatrics. 1963 Sep;32:384–388. [PubMed] [Google Scholar]
  13. Jones J. J., Lee J. The value of rats with hereditary hypothalamic diabetes insipidus for the bioassay of vasopressin. J Endocrinol. 1967 Mar;37(3):335–344. doi: 10.1677/joe.0.0370335. [DOI] [PubMed] [Google Scholar]
  14. Lauson H. D. Metabolism of antidiuretic hormones. Am J Med. 1967 May;42(5):713–744. doi: 10.1016/0002-9343(67)90091-5. [DOI] [PubMed] [Google Scholar]
  15. Miller L., Fisch L., Kleeman C. R. Relative potency of arginine-8-vasopressin and lysine-8-vasopressin in humans. J Lab Clin Med. 1967 Feb;69(2):270–291. [PubMed] [Google Scholar]
  16. PETTMAN J. G. Water intoxication due to oxytocin. Report of a case. N Engl J Med. 1963 Feb 28;268:481–482. doi: 10.1056/NEJM196302282680908. [DOI] [PubMed] [Google Scholar]
  17. RYDEN G., SJOHOLM I. Assay of oxytocin by rat mammary gland in vitro. Br J Pharmacol Chemother. 1962 Aug;19:136–141. doi: 10.1111/j.1476-5381.1962.tb01434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. SCHROEDER R., ROTT D. [On the determination and behavior of ADH in human plasma]. Klin Wochenschr. 1959 Nov 15;37:1175–1181. doi: 10.1007/BF01491358. [DOI] [PubMed] [Google Scholar]
  19. SILVER L., SCHWARTZ I. L., FONG C. T., DEBONS A. F., DAHL L. K. Disappearance of plasma radioactivity after injection of H3- or I-131-labeled arginine vasopressin. J Appl Physiol. 1961 Nov;16:1097–1099. doi: 10.1152/jappl.1961.16.6.1097. [DOI] [PubMed] [Google Scholar]
  20. Silva P., Allan M. S. Water intoxication due to high doses of synthetic oxytocin. Report of a case. Obstet Gynecol. 1966 Apr;27(4):517–520. doi: 10.1097/00006250-196604000-00013. [DOI] [PubMed] [Google Scholar]
  21. Vane J. R. The release and fate of vaso-active hormones in the circulation. Br J Pharmacol. 1969 Feb;35(2):209–242. doi: 10.1111/j.1476-5381.1969.tb07982.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vorherr H., Kleeman C. R., Hoghoughi M. Factors influencing the sensitivity of rats under ethanol anesthesia to antidiuretic hormone (ADH). Endocrinology. 1968 Feb;82(2):218–224. doi: 10.1210/endo-82-2-218. [DOI] [PubMed] [Google Scholar]

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