Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Sep;116(1):1661–1667. doi: 10.1111/j.1476-5381.1995.tb16388.x

Peripheral GABAA receptor-mediated effects of sodium valproate on dural plasma protein extravasation to substance P and trigeminal stimulation.

W S Lee 1, V Limmroth 1, C Ayata 1, F M Cutrer 1, C Waeber 1, X Yu 1, M A Moskowitz 1
PMCID: PMC1908914  PMID: 8564234

Abstract

1. The GABA transaminase inhibitor and activator of glutamic acid decarboxylase, valproic acid is being used for the treatment of migraine. Its mechanism of action is unknown. We tested the effects of sodium valproate and GABAA-agonist muscimol on dural plasma protein ([125I]-bovine serum albumin) extravasation evoked by either unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min) or substance P (SP) administration (1 nmol kg-1,i.v.) in anaesthetized Sprague-Dawley rats. 2. Intraperitoneal (i.p.) injection of sodium valproate or muscimol, but not baclofen (< or = 10 mg kg-1, i.p.) dose-dependently reduced dural plasma protein extravasation caused either by electrical trigeminal stimulation (ED50: 6.6 +/- 1.4 mg kg-1, i.p., and 58 +/- 18 micrograms kg-1, i.p. for valproate or muscimol, respectively) or by intravenous substance P administration (ED50: 3.2 +/- 1.4 mg kg-1, i.p. and 385 +/- 190 micrograms kg-1, i.p. for valproate or muscimol, respectively). 3. Valproate (6.6 mg kg-1, i.p.) or muscimol (58 micrograms kg-1, i.p.) had no effect on mean arterial blood pressure or heart rate when measured for 30 min after i.p. administration. 4. The GABAA-antagonist bicuculline (0.01 mg kg-1, i.p.) completely reversed the effect of valproate and muscimol on plasma extravasation following electrical stimulation or substance P administration, whereas the GABAB-receptor antagonist, phaclofen (0.01-1 mg kg-1, i.p.) did not. Bicuculline or phaclofen, given alone, did not alter the plasma extravasation response after either electrical stimulation or SP administration. 5. Valproate decreased plasma extravasation following substance P administration in adult animals, neonatally treated with capsaicin by a bicuculline-reversible mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1661

Selected References

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

  1. Alborch E., Torregrosa G., Terrasa J. C., Estrada C. GABA receptors mediate cerebral vasodilation in the unanesthetized goat. Brain Res. 1984 Oct 29;321(1):103–110. doi: 10.1016/0006-8993(84)90685-1. [DOI] [PubMed] [Google Scholar]
  2. Bowery N. G. GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol. 1993;33:109–147. doi: 10.1146/annurev.pa.33.040193.000545. [DOI] [PubMed] [Google Scholar]
  3. Buzzi M. G., Moskowitz M. A. The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br J Pharmacol. 1990 Jan;99(1):202–206. doi: 10.1111/j.1476-5381.1990.tb14679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buzzi M. G., Sakas D. E., Moskowitz M. A. Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater. Eur J Pharmacol. 1989 Jun 20;165(2-3):251–258. doi: 10.1016/0014-2999(89)90719-x. [DOI] [PubMed] [Google Scholar]
  5. Chi S. I., Levine J. D., Basbaum A. I. Effects of injury discharge on the persistent expression of spinal cord fos-like immunoreactivity produced by sciatic nerve transection in the rat. Brain Res. 1993 Jul 23;617(2):220–224. doi: 10.1016/0006-8993(93)91089-b. [DOI] [PubMed] [Google Scholar]
  6. Cutrer F. M., Moussaoui S., Garret C., Moskowitz M. A. The non-peptide neurokinin-1 antagonist, RPR 100893, decreases c-fos expression in trigeminal nucleus caudalis following noxious chemical meningeal stimulation. Neuroscience. 1995 Feb;64(3):741–750. doi: 10.1016/0306-4522(94)00428-8. [DOI] [PubMed] [Google Scholar]
  7. Dimitriadou V., Buzzi M. G., Moskowitz M. A., Theoharides T. C. Trigeminal sensory fiber stimulation induces morphological changes reflecting secretion in rat dura mater mast cells. Neuroscience. 1991;44(1):97–112. doi: 10.1016/0306-4522(91)90253-k. [DOI] [PubMed] [Google Scholar]
  8. Dimitriadou V., Buzzi M. G., Theoharides T. C., Moskowitz M. A. Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation. Neuroscience. 1992;48(1):187–203. doi: 10.1016/0306-4522(92)90348-6. [DOI] [PubMed] [Google Scholar]
  9. Dixon C. M., Saynor D. A., Andrew P. D., Oxford J., Bradbury A., Tarbit M. H. Disposition of sumatriptan in laboratory animals and humans. Drug Metab Dispos. 1993 Sep-Oct;21(5):761–769. [PubMed] [Google Scholar]
  10. Edvinsson L., Larsson B., Skärby T. Effect of the GABA receptor agonist muscimol on regional cerebral blood flow in the rat. Brain Res. 1980 Mar 10;185(2):445–448. doi: 10.1016/0006-8993(80)91084-7. [DOI] [PubMed] [Google Scholar]
  11. Fowler P. A., Lacey L. F., Thomas M., Keene O. N., Tanner R. J., Baber N. S. The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan. Eur Neurol. 1991;31(5):291–294. doi: 10.1159/000116756. [DOI] [PubMed] [Google Scholar]
  12. Fujiwara M., Muramatsu I. Gamma-aminobutyric acid receptor on vascular smooth muscle of dog cerebral arteries. Br J Pharmacol. 1975 Dec;55(4):561–562. doi: 10.1111/j.1476-5381.1975.tb07434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Giuliani S., Maggi C. A., Meli A. Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia. Br J Pharmacol. 1986 Jul;88(3):659–670. doi: 10.1111/j.1476-5381.1986.tb10248.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Godin Y., Heiner L., Mark J., Mandel P. Effects of DI-n-propylacetate, and anticonvulsive compound, on GABA metabolism. J Neurochem. 1969 Jun;16(3):869–873. doi: 10.1111/j.1471-4159.1969.tb08975.x. [DOI] [PubMed] [Google Scholar]
  15. Hering R., Kuritzky A. Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia. 1992 Apr;12(2):81–84. doi: 10.1046/j.1468-2982.1992.1202081.x. [DOI] [PubMed] [Google Scholar]
  16. Hering R., Kuritzky A. Sodium valproate in the treatment of cluster headache: an open clinical trial. Cephalalgia. 1989 Sep;9(3):195–198. doi: 10.1046/j.1468-2982.1989.0903195.x. [DOI] [PubMed] [Google Scholar]
  17. Hunt S. P., Kelly J. S., Emson P. C., Kimmel J. R., Miller R. J., Wu J. Y. An immunohistochemical study of neuronal populations containing neuropeptides or gamma-aminobutyrate within the superficial layers of the rat dorsal horn. Neuroscience. 1981;6(10):1883–1898. doi: 10.1016/0306-4522(81)90029-4. [DOI] [PubMed] [Google Scholar]
  18. Jancsó G., Kiraly E., Jancsó-Gábor A. Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature. 1977 Dec 22;270(5639):741–743. doi: 10.1038/270741a0. [DOI] [PubMed] [Google Scholar]
  19. Kondo E., Kiyama H., Araki T., Shida T., Ueda Y., Tohyama M. Coexpression of GABAA receptor gamma 1 and gamma 2 subunits in the rat trigeminal ganglion. Brain Res Mol Brain Res. 1994 Feb;21(3-4):363–367. doi: 10.1016/0169-328x(94)90269-0. [DOI] [PubMed] [Google Scholar]
  20. Kudrow L. The relationship of headache frequency to hormone use in migraine. Headache. 1975 Apr;15(1):36–40. doi: 10.1111/j.1526-4610.1975.hed1501036.x. [DOI] [PubMed] [Google Scholar]
  21. Lance J. W., Anthony M. Some clinical aspects of migraine. A prospective survey of 500 patients. Arch Neurol. 1966 Oct;15(4):356–361. doi: 10.1001/archneur.1966.00470160022003. [DOI] [PubMed] [Google Scholar]
  22. Lee W. S., Moussaoui S. M., Moskowitz M. A. Blockade by oral or parenteral RPR 100893 (a non-peptide NK1 receptor antagonist) of neurogenic plasma protein extravasation within guinea-pig dura mater and conjunctiva. Br J Pharmacol. 1994 Jul;112(3):920–924. doi: 10.1111/j.1476-5381.1994.tb13168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Löscher W. Valproate induced changes in GABA metabolism at the subcellular level. Biochem Pharmacol. 1981 Jun 1;30(11):1364–1366. doi: 10.1016/0006-2952(81)90323-3. [DOI] [PubMed] [Google Scholar]
  24. Magoul R., Onteniente B., Geffard M., Calas A. Anatomical distribution and ultrastructural organization of the GABAergic system in the rat spinal cord. An immunocytochemical study using anti-GABA antibodies. Neuroscience. 1987 Mar;20(3):1001–1009. doi: 10.1016/0306-4522(87)90258-2. [DOI] [PubMed] [Google Scholar]
  25. Markowitz S., Saito K., Moskowitz M. A. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J Neurosci. 1987 Dec;7(12):4129–4136. doi: 10.1523/JNEUROSCI.07-12-04129.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mathew N. T., Ali S. Valproate in the treatment of persistent chronic daily headache. An open label study. Headache. 1991 Feb;31(2):71–74. doi: 10.1111/j.1526-4610.1991.hed3102071.x. [DOI] [PubMed] [Google Scholar]
  27. Moskowitz M. A., Brody M., Liu-Chen L. Y. In vitro release of immunoreactive substance P from putative afferent nerve endings in bovine pia arachnoid. Neuroscience. 1983 Aug;9(4):809–814. doi: 10.1016/0306-4522(83)90269-5. [DOI] [PubMed] [Google Scholar]
  28. Moskowitz M. A. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci. 1992 Aug;13(8):307–311. doi: 10.1016/0165-6147(92)90097-p. [DOI] [PubMed] [Google Scholar]
  29. Moskowitz M. A., Reinhard J. F., Jr, Romero J., Melamed E., Pettibone D. J. Neurotransmitters and the fifth cranial nerve: is there a relation to the headache phase of migraine? Lancet. 1979 Oct 27;2(8148):883–885. doi: 10.1016/s0140-6736(79)92692-8. [DOI] [PubMed] [Google Scholar]
  30. Nozaki K., Moskowitz M. A., Boccalini P. CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges. Br J Pharmacol. 1992 Jun;106(2):409–415. doi: 10.1111/j.1476-5381.1992.tb14348.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ong J., Kerr D. I. GABA-receptors in peripheral tissues. Life Sci. 1990;46(21):1489–1501. doi: 10.1016/0024-3205(90)90421-m. [DOI] [PubMed] [Google Scholar]
  32. Persohn E., Malherbe P., Richards J. G. In situ hybridization histochemistry reveals a diversity of GABAA receptor subunit mRNAs in neurons of the rat spinal cord and dorsal root ganglia. Neuroscience. 1991;42(2):497–507. doi: 10.1016/0306-4522(91)90392-2. [DOI] [PubMed] [Google Scholar]
  33. Price G. W., Kelly J. S., Bowery N. G. The location of GABAB receptor binding sites in mammalian spinal cord. Synapse. 1987;1(6):530–538. doi: 10.1002/syn.890010605. [DOI] [PubMed] [Google Scholar]
  34. Rebeck G. W., Maynard K. I., Hyman B. T., Moskowitz M. A. Selective 5-HT1D alpha serotonin receptor gene expression in trigeminal ganglia: implications for antimigraine drug development. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3666–3669. doi: 10.1073/pnas.91.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Saito K., Markowitz S., Moskowitz M. A. Ergot alkaloids block neurogenic extravasation in dura mater: proposed action in vascular headaches. Ann Neurol. 1988 Dec;24(6):732–737. doi: 10.1002/ana.410240607. [DOI] [PubMed] [Google Scholar]
  36. Sluka K. A., Willis W. D., Westlund K. N. Joint inflammation and hyperalgesia are reduced by spinal bicuculline. Neuroreport. 1993 Nov 18;5(2):109–112. doi: 10.1097/00001756-199311180-00003. [DOI] [PubMed] [Google Scholar]
  37. Szabat E., Soinila S., Häppölä O., Linnala A., Virtanen I. A new monoclonal antibody against the GABA-protein conjugate shows immunoreactivity in sensory neurons of the rat. Neuroscience. 1992;47(2):409–420. doi: 10.1016/0306-4522(92)90255-z. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES