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Histamine levels and clonic convulsions of electrically-induced seizure in mice: the effects of α-fluoromethylhistidine and metoprine

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Summary

The purpose of this study was to investigate the possible role of the central histaminergic neuron system in electrically-induced seizure in mice. For this purpose, we examined the effects of intraperitoneal (i. p.) injections of histaminergic agents, such as l-histidine, metoprine, and α-fluoromethylhistidine (FMH), on electrically-induced seizure. l-Histidine decreased the duration of clonic convulsion in electrically-induced seizure, but not affected that of tonic convulsion. This effect of l-histidine was antagonized by pretreatment with FMH, indicating that it was due to histamine formed by decarboxylation of l-histidine in the central nervous system. The anticonvulsive effect of l-histidine was also reduced by the H1-antagonist pyrilamine, but not by the H2-antagonist zolantidine, indicating that the effect on electrically-induced seizure is mediated through central H1-receptors. Metoprine, which increased the histamine levels in the cerebral cortex, diencephalon and midbrain of mice, decreased the duration of clonic convulsions dose-dependently. Conversely, FMH, which decreased the brain histamine levels, increased the duration of clonic convulsions. Good inverse correlations were found between the duration of clonic convulsions and brain histamine levels, especially in the diencephalon: the histamine levels were inversely proportional to the duration of clonic convulsions. No correlation was found between the duration of tonic convulsions and brain histamine levels. These results suggest that the histaminergic neuron system is important in inhibition of the duration of clonic convulsion on electrically induced seizure in mice.

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References

  • Chen G, Ensor CR, Bohner B (1954) A facilitation action of reserpine on the central nervous system. Proc Soc Exp Biol Med 86:507–510

    Google Scholar 

  • Churchill JA, Gammon GD (1949) The effect of antihistaminic drugs on convulsive seizures. J Am Med Assoc 141:18–21

    Google Scholar 

  • Diffley D, Tran VT, Snyder SH (1980) Histamine H1-receptor labeled in vivo: antidepressants and antihistamine interactions. Eur J Pharmacol 64:177–181

    Google Scholar 

  • Duch SD, Bowers SW, Nichol CA (1978) Elevation of brain histamine levels by diaminopyrimidine inhibitors of histamine N-methyltransferase. Biochem Pharmacol 27:1507–1509

    Google Scholar 

  • Duch SD, Edelstein MP, Nichol CA (1980) Inhibition of histamine-metabolizing enzymes and elevation of histamine levels in tissues by lipid-soluble anticancer folate antagonists. Mol Pharmacol 18:100–105

    Google Scholar 

  • Fairbairn S, Sturman G (1989) The influence of central histaminergic modification on the susceptibility of mice to chemically-induced seizures. Br J Pharmacol 97 [suppl] 317

    Google Scholar 

  • Freeman P, Sturman G, Wilde P (1990) Elevation of histamine levels but not H2-receptor blockade influences electrically-induced seizure threshold in mice. J Psychopharmacol 4:313

    Google Scholar 

  • Garbarg M, Barbin G, Rodergas E, Schwartz JC (1980) Inhibition of histamine synthesis in brain by α-fluoromethylhistidine, a new irreversible inhibitor: in vitro and in vivo studies. J Neurochem 35:1045–1052

    Google Scholar 

  • Gerald MC, Richter NA (1976) Studies on the effects of histaminergic agents on seizure susceptibility in mice. Psychopharmacologia 46:277–282

    Google Scholar 

  • Hough LB, Jackowski S, Eberle N, Gagos KR, Camerota NA, Cue D (1988) Action of the brain-penetrating H2-antagonist zolantidine on histamine dynamics and metabolism in rat brain. Biochemical Pharmacol 37:4707–4711

    Google Scholar 

  • Hout J, Radouco-Thomas S, Radouco-Thomas C (1973) Qualitative and quantitative evaluation of experimentally induced seizures. In: Mercier J, Randouco-Thomas C (eds) International encyclopedia of pharmacology and therapeutics, anticonvulsant drugs, vol 1. Pergamon Press, New York, pp 125–143

    Google Scholar 

  • Kollonitsch J, Perkins LM, Patchett AA, Doldouras GA, Marburg S, Duggan DE, Maycock AL, Aster SD (1978) Selective inhibitors of biosynthesis of aminergic neurotransmitters. Nature 274:906–908

    Google Scholar 

  • Masuda Y, Shiraishi Y, Karasawa T, Yoshida K, Shimizu M (1980) Differential antagonism of anticonvulsants to various components of maximal seizures induced by electroshock or pentylentetrazol in mice. J Pharmacol Dyn 3:526–531

    Google Scholar 

  • Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214:170–197

    Google Scholar 

  • Onodera K, Ogura Y (1985) Muricidal suppression by histidine and its antagonism by α-fluoromethylhistidine in thiamine deficient rats. Jpn J Psychopharmacol 5:11–17

    Google Scholar 

  • Onodera K, Maeyama K, Watanabe T (1988) Regional changes in brain histamine levels following dietary-induced thiamine deficiency in rats. Jpn J Pharmacol 47:323–326

    Google Scholar 

  • Onodera K, Yamatodani A, Watanabe T (1992a) Effects of α-fluoromethylhistidine in locomotor activity and brain histamine and catecholamine contents of rats. Methods Find Exp Clin Pharmacol 14:97–105

    Google Scholar 

  • Onodera K, Tuomisto L, Tacke U, Airaksinen M (1992b) Strain differences in regional brain histamine levels between genetically epilepsy-prone and -resistant rats. Methods Find Exp Clin Pharmacol 14:13–16

    Google Scholar 

  • Panula P, Yang HYT, Costa E (1984) Histamine-containing neurons in the rat hypothalamus. Proc Natl Acad Sci USA 81:2572–2576

    Google Scholar 

  • Przegalinski E (1985) Monoamines and the pathophysiology of seizure disorders. In: Fray HH, Janz D (eds) Antiepileptic drugs. Handbook of experimental pharmacology, vol 74. Springer, Berlin Heidelberg New York Tokyo, pp 101–130

    Google Scholar 

  • Quach TT, Duchemin AM, Rose C, Schwartz JC (1980) Labeling of histamine H1-receptors in the brain of living mouse. Neurosci Lett 17:49–54

    Google Scholar 

  • Saper CB (1984) Diffuse cortical projection systems: anatomical organization and role in cortical function. In: MontCastle VB, Plum F, Geiger SR (ed) Handbook of physiology, the nervous system, vol 5. American Physiological Society, Bethesda, Md., pp 169–210

    Google Scholar 

  • Scherkl R, Hashem A, Frey HH (1991a) Importance of histamine seizure susceptibility. In: Timmerman H, van der Groot H (eds) New perspectives in histamine research. Birkhäuser, Basel, pp 85–89

    Google Scholar 

  • Scherkl R, Hashem A, Frey HH (1991b) Histamine in brain — its role in regulation of seizure susceptibility. Epilepsy Res 10:111–118

    Google Scholar 

  • Schwartz JC, Lampart C, Rose C (1972) Histamine formation in rat brain in vivo, effect of histidine load. J Neurochem 19:801–810

    Google Scholar 

  • Schwartz JC, Garbarg M, Pollard H (1986) Histaminergic transmission in the brain. In: Bloom FE, Mountcastle VB, Geiger SG (eds) Handbook of physiology, the nervous system, vol 4. American Physiological Society, Bethesda, Md., pp 257–316

    Google Scholar 

  • Schwartz JC, Arrang JM, Garbarg M, Pallard H, Rust M (1991) Histaminergic transmission in the mammalian brain. Physiol Rev 71:1–51

    Google Scholar 

  • Shishido S, Oishi R, Saeki K (1991) In vivo effects of some histamine H1-receptor antagonists on monoamine metabolism in the mouse brain. Naunyn-Schmiedeberg's Arch Pharmacol 343: 185–189

    Google Scholar 

  • Tuomisto L, Tacke U (1986) Is histamine an anticonvulsive inhibitory transmitter. Neuropharmaeology 25:955–958

    Google Scholar 

  • Tuomisto J, Tuomisto L (1980) Effects of histamine and histamine antagonists on the uptake and release of catecholamines and 5-HT in brain synaptosomes. Med Biol 58:33–37

    Google Scholar 

  • Wada H, Inagaki N, Yamatodani A, Watanabe T (1991) Is the histaminergic neuron system a regulatory center for whole-brain activity? Trends Neurosci 14:415–419

    Google Scholar 

  • Watanabe T, Taguchi Y, Hayashi H, Shiosaka S, Tanaka J, Kubota H, Terano Y, Tohyama M, Kubota H, Terano Y, Wada H (1984) Distribution of the histaminergic neuron system in the central nervous system of rats: a fluorescent immunohistochemical analysis with histidine decarboxylase as a marker. Brain Res 295:13–25

    Google Scholar 

  • Watanabe T, Yamatodani A, Maeyama K, Wada H (1990) Pharmacology of α-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. Trends Pharmacol Sci 11:363–367

    Google Scholar 

  • Watanabe T, Taguchi Y, Maeyama K, Wada H (1991) Formation of histamine: histidine decarboxylase. In: Uvnäs E (ed) Handbook of experimental pharmacology, vol 97, Histamine and histamine antagonists. Springer, Berlin Heidelberg New York, pp 145–163

    Google Scholar 

  • Wyngaarden JB, Seevers MH (1951) The toxic effects of antihistaminic drugs. J Am Med Assoc 145:277–283

    Google Scholar 

  • Yamatodani A, Watanabe T (1991) Studies with α-fluoromethylhistidine as a probe. In: Watanabe T, Wada H (eds) Histaminergic neurons: morphology and function. CRC Press, Boca Raton, Fl., pp 231–240

    Google Scholar 

  • Yamatodani A, Fukuda H, Iwaeda T, Wada H, Watanabe T (1985) High-performance liquid chromatographic determination of plasma and brain histamine without previous purification of biological samples: cation-exchange chromatography coupled with post-column derivatization fluorometry. J Chromatogr 344:115–123

    Google Scholar 

  • Yamatodani A, Inagaki N, Panula P, Itowi N, Watanabe T, Wada H (1991) Structure and functions of the histaminergic neuron system. In: Uvnäs E (ed) Handbook of experimental pharmacology, vol 97, histamine and histamine antagonists. Springer, Berlin Heidelberg New York, pp 243–283

    Google Scholar 

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Yokoyama, H., Onodera, K., Maeyama, K. et al. Histamine levels and clonic convulsions of electrically-induced seizure in mice: the effects of α-fluoromethylhistidine and metoprine. Naunyn-Schmiedeberg's Arch Pharmacol 346, 40–45 (1992). https://doi.org/10.1007/BF00167568

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  • DOI: https://doi.org/10.1007/BF00167568

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