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. 1979 Feb;287:519–533. doi: 10.1113/jphysiol.1979.sp012674

Effects of central administation of probenecid on fevers produced by leukocytic pyrogen and PGE2 in the rabbit.

I L Crawford, J I Kennedy, J M Lipton, S R Ojeda
PMCID: PMC1281510  PMID: 430434

Abstract

1. Single intracerebroventricular (I.C.V.) injections of probenecid (PBCD, 0.125--0.5 mg) enhanced and prolonged fever caused by I.V. administration of leukocytic pyrogen (LP) in rabbits resting in neutral (23 degrees C), cold (10 degrees C) and hot (30 degrees C) environments. Similar effects were produced by single I.C.V. injections of PBCD given before PGE2 (0.5 microgram) was injected I.C.V. in the three ambient temperatures. 2. Fever produced by IV. LP was also prolonged by infusion and by multiple injections of PBCD. 3. PBCD given I.P. (100 mg/kg) enhanced and prolonged fever caused by I.V. injection of Salmonella typhosa endotoxin. 4. Hyperthermia produced by I.C.V. PGE2 was not augmented by subsequent PBCD infusion. However, pre-treatment with PBCD followed by PGE2 injection and PBCD infusion caused hyperthermia that was very high and prolonged, and, in some cases, lethal. 5. Acetaminophen (2 mg, I.C.V.) and indomethacin (10 mg/kg, I.V.) lowered body temperature when given during fever induced by LP and prolonged by PBCD infusion. 6. The concentration of PGE in cerebrospinal fluid (c.s.f.) samples taken from the third or lateral ventricles rose or stabilized during PBCD infusions made during LP fever. However, similar changes in PGE concentration also occurred during control infusions when body temperature was low. 7. We conclude that termination of the actions of both central endogenous pyrogen and centrally administered PGE2, and the subsequent reduction of fevers produced by them, require a PBCD-sensitive facilitated transport system. The reduction of PBCD-prolonged PL fevers by antipyretics which block PGE synthesis suggests that prolongation by PBCD of LP fever is not due to blockade of PGE transport in a subsequent step in fever mediation per se, but is due to inhibition of transport of LP itself, or of other mediators associated with it.

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Selected References

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  1. Bauminger S., Zor U., Lindner H. R. Radioimmunological assay of prostaglandin synthetase activity. Prostaglandins. 1973 Sep;4(3):313–324. doi: 10.1016/0090-6980(73)90019-1. [DOI] [PubMed] [Google Scholar]
  2. Bito L. Z., Davson H., Hollingsworth J. R. Facilitated transport of prostaglandins across the blood-cerebrospinal fluid and blood-brain barriers. J Physiol. 1976 Apr;256(2):273–285. doi: 10.1113/jphysiol.1976.sp011325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bito L. Z., Davson H., Salvador E. V. Inhibition of in vitro concentrative prostaglandin accumulation by prostaglandins, prostaglandin analogues and by some inhibitors of organic anion transport. J Physiol. 1976 Apr;256(2):257–271. doi: 10.1113/jphysiol.1976.sp011324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bodel P. T., Wechsler A., Atkins E. Comparison of endogenous pyrogens from human and rabbit leucocytes utilizing Sephadex filtration. Yale J Biol Med. 1969 Apr;41(5):376–387. [PMC free article] [PubMed] [Google Scholar]
  5. CAMERON G. Secretory activity of the chorioid plexus in tissue culture. Anat Rec. 1953 Sep;117(1):115–125. doi: 10.1002/ar.1091170109. [DOI] [PubMed] [Google Scholar]
  6. Clark W. G., Cumby H. R. The antipyretic effect of indomethacin. J Physiol. 1975 Jul;248(3):625–638. doi: 10.1113/jphysiol.1975.sp010992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cranston W. I., Duff G. W., Hellon R. F., Mitchell D., Townsend Y. Evidence that brain prostaglandin synthesis is not essential in fever. J Physiol. 1976 Jul;259(1):239–249. doi: 10.1113/jphysiol.1976.sp011464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cranston W. I., Hellon R. F., Mitchell D. A dissociation between fever and prostaglandin concentration in cerebrospinal fluid. J Physiol. 1975 Dec;253(2):583–592. doi: 10.1113/jphysiol.1975.sp011208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crawford I. L., Kennedy J. I., Lipton J. M. Simple "planilabe" for rapid establishment of the stereotaxic horizontal zero plane in rabbits. Brain Res Bull. 1977 Sep-Oct;2(5):397–398. doi: 10.1016/0361-9230(77)90075-2. [DOI] [PubMed] [Google Scholar]
  10. Cutler R. W., Lorenzo A. V. Transport of 1-aminocyclopentanecarboxylic acid from feline cerebrospinal fluid. Science. 1968 Sep 27;161(3848):1363–1364. doi: 10.1126/science.161.3848.1363. [DOI] [PubMed] [Google Scholar]
  11. Cutler R. W. Transport of lysine from cerebrospinal fluid of the cat. J Neurochem. 1970 Jul;17(7):1017–1027. doi: 10.1111/j.1471-4159.1970.tb02255.x. [DOI] [PubMed] [Google Scholar]
  12. Davson H. Review lecture. The blood-brain barrier. J Physiol. 1976 Feb;255(1):1–28. doi: 10.1113/jphysiol.1976.sp011267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dinarello C. A., Goldin N. P., Wolff S. M. Demonstration and characterization of two distinct human leukocytic pyrogens. J Exp Med. 1974 Jun 1;139(6):1369–1381. doi: 10.1084/jem.139.6.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Feldberg W., Gupta K. P., Milton A. S., Wendlandt S. Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats. J Physiol. 1973 Oct;234(2):279–303. doi: 10.1113/jphysiol.1973.sp010346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Feldberg W., Gupta K. P. Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid. J Physiol. 1973 Jan;228(1):41–53. doi: 10.1113/jphysiol.1973.sp010071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feldberg W., Saxena P. N. Fever produced by prostaglandin E1. J Physiol. 1971 Sep;217(3):547–556. doi: 10.1113/jphysiol.1971.sp009585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fishman R. A. Blood-brain and CSF barriers to penicillin and related organic acids. Arch Neurol. 1966 Aug;15(2):113–124. doi: 10.1001/archneur.1966.00470140003001. [DOI] [PubMed] [Google Scholar]
  18. Guldberg H. C., Ashcroft G. W., Crawford T. B. Concentrations of 5-hydroxyindolylacetic acid and homovanillic acid in the cerebrospinal fluid of the dog before and during treatment with probenecid. Life Sci. 1966 Sep;5(17):1571–1575. doi: 10.1016/0024-3205(66)91026-5. [DOI] [PubMed] [Google Scholar]
  19. Harris W. S., Lipton J. M. Intracerebroventricular taurine in rabbits: effects of normal body temperature, endotoxin fever and hyperthermia produced by PGE1 and amphetamine. J Physiol. 1977 Apr;266(2):397–410. doi: 10.1113/jphysiol.1977.sp011773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Karoum F., Bunney W., Jr, Gillin J. C., Jimerson D., Van Kammen D., Wyatt R. J. Effect of probenecid on the concentration of the lumbar cerebrospinal fluid acidic metabolites of tyramine, octopamine, dopamine and norepinephrine. Biochem Pharmacol. 1977 Apr 1;26(7):629–632. doi: 10.1016/0006-2952(77)90036-3. [DOI] [PubMed] [Google Scholar]
  21. Lipton J. M., Romans W. E. Modification of rabbit head holder to increase speed and accuracy of stereotaxic surgery. Brain Res Bull. 1976 Jan-Feb;1(1):159–160. doi: 10.1016/0361-9230(76)90059-9. [DOI] [PubMed] [Google Scholar]
  22. Lipton J. M., Ticknor C. B. Central effect of taurine and its analogues on fever caused by intravenous leukocytic pyrogen in the rabbit. J Physiol. 1979 Feb;287:535–543. doi: 10.1113/jphysiol.1979.sp012675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Milton A. S., Wendlandt S. Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol. 1971 Oct;218(2):325–336. doi: 10.1113/jphysiol.1971.sp009620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nakano J., Prancan A. V., Moore S. E. Metabolism of prostaglandin E 1 in the cerebral cortex and cerebellum of the dog and rat. Brain Res. 1972 Apr 28;39(2):545–548. doi: 10.1016/0006-8993(72)90462-3. [DOI] [PubMed] [Google Scholar]
  25. Ojeda S. R., Naor Z., McCann S. M. Prostaglandin E levels in hypothalamus, median eminence and anterior pituitary of rats of both sexes. Brain Res. 1978 Jun 23;149(1):274–277. doi: 10.1016/0006-8993(78)90611-x. [DOI] [PubMed] [Google Scholar]
  26. RALL D. P., SHELDON W. Transport of organic acid dyes by the isolated choroid plexus of the spiny dogfish S. acanthias. Biochem Pharmacol. 1962 Feb;11:169–170. doi: 10.1016/0006-2952(62)90107-7. [DOI] [PubMed] [Google Scholar]
  27. SAWYER C. H., EVERETT J. W., GREEN J. D. The rabbit diencephalon in stereotaxic coordinates. J Comp Neurol. 1954 Dec;101(3):801–824. doi: 10.1002/cne.901010307. [DOI] [PubMed] [Google Scholar]
  28. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  29. Westergaard E., Brightman M. W. Transport of proteins across normal cerebral arterioles. J Comp Neurol. 1973 Nov 1;152(1):17–44. doi: 10.1002/cne.901520103. [DOI] [PubMed] [Google Scholar]

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