Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 337, Issue 4, pp 423–428 | Cite as

Enhancement of blood-brain barrier permeability to sodium fluorescein by stimulation of µ opioid receptors in mice

  • Miwa Baba
  • Ryozo Oishi
  • Kiyomi Saeki
Article

Summary

The effects of opioids on the permeability of the blood-brain barrier (BBB) were examined in mice with sodium fluorescein as an indicator of the permeability. The brain was perfused with saline 30 min after injection of sodium fluorescein (40 mg/kg, i. v.) and examined by fluorometry. Morphine hydrochloride (0.3–10 mg/kg, s. c.) markedly increased the brain level of sodium fluorescein dose-dependently without influencing the plasma level, when administered 20 min before sodium fluorescein injection. Intracerebroventricularly (i. c. v.) injected morphine hydrochloride (0.5 and 1.0 Erg) increased the brain sodium fluorescein level. Buprenorphine (0.1 and 0.5 mg/kg, s. c.) was also effective. However, pentazocine, ethylketazocine, U-50488H and SKF-10047 had no significant influence. The i.c.v. administration of [D-Ala2, McPhe4, Gly(ol)5]enkephalin (0.1 μg) and [D-Ala2, D-Leu5]enkephalin (0.5 μg) but not of [D-Thr2, Leu5]enkephalin-Thr increased the brain level of sodium fluorescein significantly. A small dose of naloxone (i. p.) significantly inhibited the effects of morphine, buprenorphine, [D-Ala2, McPhe4, Gly(ol)5]enkephalin and [D-Ala3, D-Leu5]enkephalin. ICI-174864 co-administered i. c. v. with [D-Ala2, D-Leu5]enkephalin was ineffective in antagonizing the effect of the latter. These findings suggest that the stimulation of µ opioid receptors results in an increase in BBB permeability to sodium fluorescein.

Key words

Morphine Blood-brain barrier Sodium fluorescein Opioids Buprenorphine [D-Ala2, McPhe4, Gly(ol)5]enkephalin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brase DA, Iwamoto ET, Loh HH, Way EL (1976) Reinitiation of sensitivity to naloxone by a single narcotic injection in postaddicted mice. J Pharmacol Exp Ther 197:317–325Google Scholar
  2. Corbett AD, Gillan MGC, Kosterlitz HW, McKnight AT, Paterson SJ, Robson LE (1984) Selectivities of opioid peptide analogues as agonists and antagonists at the δ-receptor. Br J Pharmacol 83:271–279Google Scholar
  3. Cotton R, Giles MG, Miller L, Shaw SJ, Timms D (984) ICI 174864: A highly selective antagonist for the opioid δ-receptor. Eur J Pharmacol 97:331–332Google Scholar
  4. Domer FR, Boertje SB, Bing EG, Reddix I (1983) Histamine- and acetylcholine-induced changes in the permeability of the blood-brain of normotensive and spontaneously hypertensive rats. Neuropharmacology 22:615–619Google Scholar
  5. Domino EF (1979) Opiate interaction with cholinergic neurons. Adv Biochem Psychopharmacol 20:339–355Google Scholar
  6. Duckles SP (1981) Evidence for a functional cholinergic innervation of cerebral arteries. J Pharmacol Exp Ther 217:544–548Google Scholar
  7. Fukui K, Shiomi H, Takagi H (1972) Effect of morphine on tyrosine hydroxylase activity in mouse brain. Eur J Pharmacol 19:123–125Google Scholar
  8. Goldstein AJames IF (1984) Multiple opioid receptors: Criteria for identification and classification. Trends Pharmacol Sci 5:503–505Google Scholar
  9. Gulati A, Nath C, Shanker K, Dhawan KN, Bhargava KP (1982) Fluorescein spectrophotofluorometry: A sensitive quantitative method for evaluating the blood brain barrier. Pharmacol Res Commun 14:649–661Google Scholar
  10. Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol 12:12–15Google Scholar
  11. Handa BK, Lane AC, Lord JAH, Morgan BA, Rance MJ, Smith CFC (1981) Analogues of β-LPH 61–64 possessing selective agonist activity at µ-opiate receptors. Eur J Pharmacol 70:531–540Google Scholar
  12. Heyman JS, Mulvaney SA, Mosberg HI, Porreca F (1987) Opioid αreceptor involvement in supraspinal and spinal antinociception in mice. Brain Res 420:100–108Google Scholar
  13. Hoffman HJ, Olszewski J (1961) Spread of sodium fluorescein in normal brain tissue. Neurology 11:1081–1085Google Scholar
  14. Jaffe JH, Martin WR (1985) Opioid analgesics and antagonists. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics. MacMillan, New York, pp 491- 531Google Scholar
  15. Kobayashi H, Magnoni MS, Govoni S, Izumi F, Wada A, Trabucchi M (1985) Neural control of brain microvessel function. Experimentia 41:427–434Google Scholar
  16. Lahti RA, Von Voightlander, Barsuhn C (1982) Properties of a selective kappa agonist. U-50,488H. Life Sci 31:2257–2260Google Scholar
  17. Lange DC, Fujimoto JM, Roerig S, Wang RIH (1977) Enhanced naloxone distribution to the brain by morphine pretreatment in mice. Drug Metab Disp 5:167–173Google Scholar
  18. Magnan J, Paterson SJ, Tavani A, Kosterlitz HW (1982) The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn-Schmiedeberg's Arch Pharmacol 319:197–205Google Scholar
  19. McGilliard KL, Takemori AE (1978) Alterations in the antagonism by naloxone of morphine-induced respiratory depression and analgesia after morphine pretreatment. J Pharmacol Exp Ther 207:884–991Google Scholar
  20. Nishibori M, Oishi R, Itoh Y, Saeki K (1985) Morphine-induced changes in histamine dynamics in mouse brain. J Neurochem 45:719–724Google Scholar
  21. Oishi R, Ozaki M, Takemori A (1983) In vivo binding of naloxone to opioid receptors in morphine-dependent mice. Neuropharmacology 22:1015–1019Google Scholar
  22. Paterson SJ, Magnan J, Tavani A, Kosterlitz HW (1981) In: Takagi H, Simon EJ (eds) Advances in endogenous and exogenous opioids. Kodansha, Tokyo, pp 2–4Google Scholar
  23. Patrick GA, Dewey WL, Spaulding TC, Harris LS (1975) Relationship of brain morphine levels to analgesic activity in acutely treated mice and rats and in pellet-implanted mice. J Pharmacol Exp Ther 193:876–883Google Scholar
  24. Pert CB, Snyder SH (1975) Identification of opiate receptor binding in intact animals. Life Sci 16:1623–1634Google Scholar
  25. Preskorn SH, Hartman BK, Raichle ME, Clark HB (1980) The effect of dibenzazepines (tricyclic antidepressants) on cerebral capillary permeability in the rat in vitro. J Pharmacol Exp Ther 213:313–320Google Scholar
  26. Raichle ME, Hartman BK, Eichling JO, Sharpe LG (1975) Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Natl Acad Sci USA 72:3726–3730Google Scholar
  27. Reinhard JF, Liebman JE, Schlosberg AJ, Moskowitz MA (1979) Serotonin neurons project to small blood vessels in the brain. Science (Wash) 206:85–87Google Scholar
  28. Smith CB, Sheldon MI, Bednarczyk JH, Villarreal JE (1972) Morphine-induced increase in the incorporation of 14-C-tyrosine into 14-C-dopamine and 14-C-norepinephrine in the mouse brain, antagonism by naloxone and tolerance. J Pharmacol Exp Ther 180:547–557Google Scholar
  29. Takemori AE, Ikeda M, Portoghese PS (1986) The µ, κ and δ properties of various opioid agonists. Eur J Pharmacol 123:357–361Google Scholar
  30. Tervo T, Joo F, Palkama A, Salminen L (1979) Penetration barrier to sodium fluorescein and fluorescein-labelled dextrans of various molecular sizes in brain capillaries. Experimentia 35:252–254Google Scholar
  31. Wolman M, Klatzo I, Chui E, Wilmes F, Nishimoto K, Fujiwara K, Spatz M (1981) Evaluation of the dye-protein tracers in pathophysiology of the blood-brain barrier. Acta Neuropathol 54:55–61Google Scholar
  32. Yarbrough GG, Buxbaum DM, Sanders-Busch E (1972) Increased serotonin turnover in acutely morphine-treated mice. Biochem Pharmacol 21:2667–2669Google Scholar
  33. Zajac JM, Gacel G, Petit F, Dodey P, Rossignol P, Rogues BP (1983) Deltakephalin, Tyr-DThr-Gly-Phe-Leu-Thr: A new highly potent and fully specific agonist for 6-receptors. Biochem Biophys Res Commun 111:390–397Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Miwa Baba
    • 1
  • Ryozo Oishi
    • 1
  • Kiyomi Saeki
    • 1
  1. 1.Department of PharmacologyOkayama University Medical SchoolOkayamaJapan

Personalised recommendations