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. 1971 Jun;50(6):1301–1308. doi: 10.1172/JCI106609

Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and 5-formyltetrahydrofolate

M Levitt 1,2,3, P F Nixon 1,2,3, J H Pincus 1,2,3, J R Bertino 1,2,3
PMCID: PMC292061  PMID: 5314166

Abstract

Serum disappearance curves in dogs after the intravenous injection of radioactive methotrexate, 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and folic acid followed first-order kinetics with half-disappearance times ranging from 1.3 to 9 hr respectively. Equilibration of spinal fluid tritium levels with those in serum was rapid (3.0 hr) for both of the reduced folates but was not observed at any time after folic acid and methotrexate. The only radioactive folate identified in the spinal fluid after intravenous injection of either 5-formyltetrahydrofolate or folic acid, as well as 5-methyltetrahydrofolate was 5-methyltetrahydrofolate. These findings indicated that 5-methyltetrahydrofolate was taken up preferentially into the spinal fluid and that the other folate congeners were converted to this compound before uptake. Diphenylhydantoin administration did not alter the uptake of 5-methyltetrahydrofolate into the spinal fluid but was associated with reduced renal excretion of this compound.

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Selected References

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

  1. Allen C. D., Klipstein F. A. Brain folate concentration in folate-deficient rats receiving diphenylhydantoin. Neurology. 1970 Apr;20(4):403–403. [PubMed] [Google Scholar]
  2. Arakawa T., Narisawa K., Tanno K., Hirooka Y., Ono T. Megaloblastic anemia and mental retardation associated with hyperfolic-acidemia: probably due to N5 methyltetrahydrofolate transferase deficiency. Tohoku J Exp Med. 1967 Sep;93(1):1–22. doi: 10.1620/tjem.93.1. [DOI] [PubMed] [Google Scholar]
  3. BECKER B. Cerebrospinal fluid iodide. Am J Physiol. 1961 Dec;201:1149–1151. doi: 10.1152/ajplegacy.1961.201.6.1149. [DOI] [PubMed] [Google Scholar]
  4. BRODIE B. B., HOGBEN C. A. Some physico-chemical factors in drug action. J Pharm Pharmacol. 1957 Jun;9(6):345–380. doi: 10.1111/j.2042-7158.1957.tb12289.x. [DOI] [PubMed] [Google Scholar]
  5. Berlin R. D. Purines: active transport by isolated choroid plexus. Science. 1969 Mar 14;163(3872):1194–1195. doi: 10.1126/science.163.3872.1194. [DOI] [PubMed] [Google Scholar]
  6. HERBERT V., LARRABEE A. R., BUCHANAN J. M. Studies on the identification of a folate compound of human serum. J Clin Invest. 1962 May;41:1134–1138. doi: 10.1172/JCI104565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. JOHNS D. G., HOLLINGSWORTH J. W., CASHMORE A. R., PLENDERLEITH I. H., BERTINO J. R. METHOTREXATE DISPLACEMENT IN MAN. J Clin Invest. 1964 Apr;43:621–629. doi: 10.1172/JCI104947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jensen O. N., Olesen O. V. Folic acid concentrations in psychiatric patients. Acta Psychiatr Scand. 1969;45(3):289–294. doi: 10.1111/j.1600-0447.1969.tb07129.x. [DOI] [PubMed] [Google Scholar]
  9. KLIPSTEIN F. A. SUBNORMAL SERUM FOLATE AND MACROCYTOSIS ASSOCIATED WITH ANTICONVULSANT DRUG THERAPY. Blood. 1964 Jan;23:68–86. [PubMed] [Google Scholar]
  10. Lanzkowsky P., Erlandson M. E., Bezan A. I. Isolated defect of folic acid absorption associated with mental retardation and cerebral calcification. Blood. 1969 Oct;34(4):452–465. [PubMed] [Google Scholar]
  11. Rubin R., Owens E., Rall D. Transport of methotrexate by the choroid plexus. Cancer Res. 1968 Apr;28(4):689–694. [PubMed] [Google Scholar]
  12. Schrumpf E., Bjelke E. Vitamin B 12 in the serum and the cerebrospinal fluid. Acta Neurol Scand. 1970;46(2):243–248. doi: 10.1111/j.1600-0404.1970.tb05620.x. [DOI] [PubMed] [Google Scholar]
  13. Strachan R. W., Henderson J. G. Dementia and folate deficiency. Q J Med. 1967 Apr;36(142):189–204. [PubMed] [Google Scholar]
  14. Weckman N., Lehtovaara R. Logarithmic-normal distribution of cerebrospinal fluid folate concentrations. Experientia. 1969 Jun 15;25(6):585–586. doi: 10.1007/BF01896524. [DOI] [PubMed] [Google Scholar]
  15. Wells D. G., Casey H. J. Lactobacillus casei C.S.F. folate activity. Br Med J. 1967 Sep 30;3(5569):834–836. doi: 10.1136/bmj.3.5569.834. [DOI] [PMC free article] [PubMed] [Google Scholar]

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