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. 1989 Apr;86(7):2483–2487. doi: 10.1073/pnas.86.7.2483

Prostaglandin E2 and its methyl ester reduce cataplexy in canine narcolepsy.

S Nishino 1, E Mignot 1, B Fruhstorfer 1, W C Dement 1, O Hayaishi 1
PMCID: PMC286937  PMID: 2928344

Abstract

The effects of intravenous administration of prostaglandins (PGs) were investigated in genetically narcoleptic Doberman pinschers. The treatment of narcoleptic dogs with PGE2 and PGE2 methyl ester, but not PGD2 and PGD2 methyl ester, induced a dose-dependent reduction of canine cataplexy, a dissociated manifestation of rapid-eye-movement sleep. The effect was specific and not associated with any change in other behavior. Furthermore, the effect was long-lasting (up to 2 hr) and could not be explained by the acute cardiovascular changes seen after intravenous PG administration. PGE2 methyl ester, a lipophilic derivative of PGE2 with more central penetration than PGE2, was 4 times more potent than PGE2. These results indicate that PGE2 modifies cataplexy through a central effect and suggest that this prostaglandin may play a role in rapid-eye-movement sleep regulation.

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Selected References

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

  1. Babcock D. A., Narver E. L., Dement W. C., Mitler M. M. Effects of imipramine, chlorimipramine, and fluoxetine on cataplexy in dogs. Pharmacol Biochem Behav. 1976 Dec;5(6):599–602. doi: 10.1016/0091-3057(76)90298-7. [DOI] [PubMed] [Google Scholar]
  2. Delashaw J. B., Jr, Foutz A. S., Guilleminault C., Dement W. C. Cholinergic mechanisms and cataplexy in dogs. Exp Neurol. 1979 Dec;66(3):745–757. doi: 10.1016/0014-4886(79)90218-8. [DOI] [PubMed] [Google Scholar]
  3. Eguchi N., Hayashi H., Urade Y., Ito S., Hayaishi O. Central action of prostaglandin E2 and its methyl ester in the induction of hyperthermia after their systemic administration in urethane-anesthetized rats. J Pharmacol Exp Ther. 1988 Nov;247(2):671–679. [PubMed] [Google Scholar]
  4. Foutz A. S., Delashaw J. B., Jr, Guilleminault C., Dement W. C. Monoaminergic mechanisms and experimental cataplexy. Ann Neurol. 1981 Oct;10(4):369–376. doi: 10.1002/ana.410100409. [DOI] [PubMed] [Google Scholar]
  5. Goodwin J. S., Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol. 1983 Oct;3(4):295–315. doi: 10.1007/BF00915791. [DOI] [PubMed] [Google Scholar]
  6. Hayaishi O. Sleep-wake regulation by prostaglandins D2 and E2. J Biol Chem. 1988 Oct 15;263(29):14593–14596. [PubMed] [Google Scholar]
  7. Hobson J. A., Goldberg M., Vivaldi E., Riew D. Enhancement of desynchronized sleep signs after pontine microinjection of the muscarinic agonist bethanechol. Brain Res. 1983 Sep 19;275(1):127–136. doi: 10.1016/0006-8993(83)90424-9. [DOI] [PubMed] [Google Scholar]
  8. Honda Y., Juji T., Matsuki K., Naohara T., Satake M., Inoko H., Someya T., Harada S., Doi Y. HLA-DR2 and Dw2 in narcolepsy and in other disorders of excessive somnolence without cataplexy. Sleep. 1986;9(1 Pt 2):133–142. doi: 10.1093/sleep/9.1.133. [DOI] [PubMed] [Google Scholar]
  9. Inoué S., Honda K., Komoda Y., Uchizono K., Ueno R., Hayaishi O. Differential sleep-promoting effects of five sleep substances nocturnally infused in unrestrained rats. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6240–6244. doi: 10.1073/pnas.81.19.6240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Matsumura H., Goh Y., Ueno R., Sakai T., Hayaishi O. Awaking effect of PGE2 microinjected into the preoptic area of rats. Brain Res. 1988 Mar 22;444(2):265–272. doi: 10.1016/0006-8993(88)90935-3. [DOI] [PubMed] [Google Scholar]
  11. Mignot E., Guilleminault C., Bowersox S., Rappaport A., Dement W. C. Effect of alpha 1-adrenoceptors blockade with prazosin in canine narcolepsy. Brain Res. 1988 Mar 15;444(1):184–188. doi: 10.1016/0006-8993(88)90927-4. [DOI] [PubMed] [Google Scholar]
  12. Mignot E., Guilleminault C., Bowersox S., Rappaport A., Dement W. C. Role of central alpha-1 adrenoceptors in canine narcolepsy. J Clin Invest. 1988 Sep;82(3):885–894. doi: 10.1172/JCI113694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mitler M. M., Dement W. C. Sleep studies on canine narcolepsy: pattern and cycle comparisons between affected and normal dogs. Electroencephalogr Clin Neurophysiol. 1977 Nov;43(5):691–699. doi: 10.1016/0013-4694(77)90084-0. [DOI] [PubMed] [Google Scholar]
  14. Monti J. M. Minireview. Catecholamines and the sleep-wake cycle. II. REM sleep. Life Sci. 1983 Mar 28;32(13):1401–1415. doi: 10.1016/0024-3205(83)90905-0. [DOI] [PubMed] [Google Scholar]
  15. Ogorochi T., Narumiya S., Mizuno N., Yamashita K., Miyazaki H., Hayaishi O. Regional distribution of prostaglandins D2, E2, and F2 alpha and related enzymes in postmortem human brain. J Neurochem. 1984 Jul;43(1):71–82. doi: 10.1111/j.1471-4159.1984.tb06680.x. [DOI] [PubMed] [Google Scholar]
  16. Onoe H., Ueno R., Fujita I., Nishino H., Oomura Y., Hayaishi O. Prostaglandin D2, a cerebral sleep-inducing substance in monkeys. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4082–4086. doi: 10.1073/pnas.85.11.4082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Suzuki F., Hayashi H., Ito S., Hayaishi O. Methyl ester of prostaglandin D2 as a delivery system of prostaglandin D2 into brain. Biochim Biophys Acta. 1987 Feb 14;917(2):224–230. [PubMed] [Google Scholar]
  18. Tokumoto H., Watanabe K., Fukushima D., Shimizu T., Hayaishi O. An NADP-linked 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin D2 from swine brain. J Biol Chem. 1982 Nov 25;257(22):13576–13580. [PubMed] [Google Scholar]
  19. Urade Y., Fujimoto N., Kaneko T., Konishi A., Mizuno N., Hayaishi O. Postnatal changes in the localization of prostaglandin D synthetase from neurons to oligodendrocytes in the rat brain. J Biol Chem. 1987 Nov 5;262(31):15132–15136. [PubMed] [Google Scholar]
  20. Watanabe Y., Watanabe Y., Hayaishi O. Quantitative autoradiographic localization of prostaglandin E2 binding sites in monkey diencephalon. J Neurosci. 1988 Jun;8(6):2003–2010. doi: 10.1523/JNEUROSCI.08-06-02003.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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