Early in this century, histamine (imidazolethylamine) was detected by Sir Henry Dale and his co-workers as a uterine stimulant in extracts of contaminated ergot (Barger and Dale, 1910). In the following years, its potent effects on smooth muscle and its participation in the allergic response were established. Although originally suspected to be the result of bacterial action during putrefaction, the compound was later successfully isolated from several types of fresh tissue and was therefore given the name histamine, which is derived from the Greek word histos for tissue. In 1943, using the guinea pig ileum as bioassay, Kwiatkowski detected histamine in brain and observed that there was a higher concentration in the grey than in the white matter. More sensitive methods for the determination of histamine were subsequently developed, including fluorometric and enzymatic-isotopic assays, but until very recently it has not been possible to directly visualize histaminergic neurons in brain. Thus, histamine has attracted less attention among neurobiologists than other biogenic amines, although evidence that it acts as a neurotransmitter is at least as good (Green, 1970; Green et al., 1978, Schwartz et al., 1985).


Histamine Receptor Medial Forebrain Bundle Histidine Decarboxylase Calcium Spike Histaminergic Neuron 
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  1. Anderson, E. G., Haas, H. L., and Hösli, L., 1973, Comparison of effects of noradrenaline and histamine with cyclic AMP on brain stem neurones, Brain Res. 49: 471–475.PubMedCrossRefGoogle Scholar
  2. Arrang, J.-M., Garbarg, M., and Schwartz, J. C., 1983, Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor, Nature. 302: 832–837.PubMedCrossRefGoogle Scholar
  3. Barger, G., and Dale, H. H., 1910, Die physiologische Wirkung einer Secalebase und deren Identifizierung als Imidazolaethylamin, Z. Physiol. 24: 885–889.Google Scholar
  4. Barker, J. L., Crayton, J. W., and Nicoll, R. A., 1971, Noradrenaline and acetylcholine responses of supraoptic neurosecretory cells, J. Physiol. (Lond.) 218: 19–32.Google Scholar
  5. Baudry, M., Martres, M. P., and Schwartz, J. C., 1973, The subcellular localisation of histidine decarboxylase in various regions of rat brain, J. Neurochem. 21: 1301–1309.PubMedCrossRefGoogle Scholar
  6. Ben-Ari, Y., Le Gal la Salle, G., Barbin, G., Schwartz, J. C., and Garbarg, M., 1977, Histamine synthesizing afferents within the amygdaloid complex and bed nucleus of the stria terminalis of the rat, Brain Res. 138: 285–294.PubMedCrossRefGoogle Scholar
  7. Bennett, C. T., and Pert, A., 1974, Antidiuresis produced by injections of histamine into the cat supraoptic nucleus, Brain Res. 78: 151–156.PubMedCrossRefGoogle Scholar
  8. Black, J. W., Duncan, W. A. M., Durant, C. J., Ganellin, C. R., and Parsons, E. M., 1972, Definition and antagonism of histamine Hz-receptors, Nature. 236: 385–390.PubMedCrossRefGoogle Scholar
  9. Brimble, M. J., and Wallis, D. I., 1973, Histamine H1 and Hz-receptors at a ganglionic synapse, Nature. 246: 156–158.PubMedCrossRefGoogle Scholar
  10. Brown, D. A., and Griffith, W. H., 1983, Calcium-activated outward current in voltage clamped hippocampal neurones of the guinea-pig, J. Physiol. (Lund.) 337: 287–301.Google Scholar
  11. Brownstein, M. J., Saavedra, J. M., Axelrod, J., Zeman, G. H., and Carpenter, D. O., 1974a, Coexistence of several putative neurotransmitters in single identified neurons of aplysia, Proc. Natl. Acad. Sci. USA 71: 4662–4665.PubMedCrossRefGoogle Scholar
  12. Brownstein, M. J., Saavedra, J. M., Palkovits, M., and Axelrod, J., 1974b, Histamine content of hypothalamic nuclei of the rat, Brain Res. 77: 151.PubMedCrossRefGoogle Scholar
  13. Carette, B., 1978, Responses of preoptic-septal neurons to iontophoretically applied histamine, Brain Res. 145: 391–395.PubMedCrossRefGoogle Scholar
  14. Carpenter, D. O., and Gaubatz, G. L., 1975, H1 and HZ histamine receptors on aplysia neurones, Nature. 254: 343–344.PubMedCrossRefGoogle Scholar
  15. Chang, R. S. L., Tran, V. T., and Snyder, S. H., 1979, Heterogeneity of histamine H1-receptors: Species variations in (3H) mepyramine binding of brain membranes, J. Neurochem. 32: 1653–1663.PubMedCrossRefGoogle Scholar
  16. Claiborne, B. J., and Selverston, A. I., 1984, Histamine as a neurotransmitter in the stomatogastric nervous system of the spiny lobster, J. Neurosci. 4: 708–721.PubMedGoogle Scholar
  17. Daly, J. W., 1976, The nature of receptors regulating the formation of cyclic AMP in brain tissue, Life Sci. 18: 1349–1358.PubMedCrossRefGoogle Scholar
  18. Dismukes, K., and Snyder, S. H., 1974, Dynamics of brain histamine, Adv. Neurol. 5: 101–109.PubMedGoogle Scholar
  19. Engberg, I., Flatman, J. A., and Kadzielawa, K., 1976, Lack of specificity of motoneurone responses to microiontophoretically applied phenolic amines, Acta Physiol. Scand. 96: 137–139.PubMedCrossRefGoogle Scholar
  20. Etgen, A. M., and Browning, E. T., 1983, Activators of cyclic AMP accumulation in rat hippocampal slices: Action of vasoactive intestinal peptide (VIP), J. Neurosci. 3: 2487–2493.PubMedGoogle Scholar
  21. Gajtkowski, G. A., Norris, D. B., Rising, T. J., and Wood, T. P., 1983, Specific binding of Htiotidine to histamine H2-receptors in guinea pig cerebral cortex, Nature. 304: 65–67.PubMedCrossRefGoogle Scholar
  22. Garbarg, M., Barbin, G., Feger, J., and Schwartz, J. C., 1974, Histaminergic pathway in rat brain evidenced by lesions of the medial forebrain bundle, Science. 186: 833–835.PubMedCrossRefGoogle Scholar
  23. Garbarg, M., Barbin, G., Rodergas, E., and Schwartz, J. C., 1980, Inhibition of histamine synthesis in brain by alpha-fluoromethylhistidine, a new irreversible inhibitor: in vitro and in vivo studies, J. Neurochem. 35: 1045–1052.PubMedCrossRefGoogle Scholar
  24. Geller, H. M., 1976, Effects of some putative neurotransmitters on unit activity of tuberai hypothalamic neurons in vitro, Brain Res. 108: 423–430.PubMedCrossRefGoogle Scholar
  25. Geller, H. M., 1979, Are histamine H2-receptor depressions of neuronal activity in tissue cultures of rat hypothalamus mediated through cyclic adenosine monophosphate? Neurosci. Lett. 14: 49–53.PubMedCrossRefGoogle Scholar
  26. Geller, H. M., 1981, Histamine actions on activity of cultured hypothalamic neurons: Evidence for mediation by H1 and H2 histamine receptors, Dev. Brain Res. 1: 89–101.CrossRefGoogle Scholar
  27. Gotow, T., Kirkpatrick, C. T., and Tomita, T., 1980, Excitatory and inhibitory effects of histamine on molluscan neurons, Brain Res. 196: 151–167.PubMedCrossRefGoogle Scholar
  28. Green, J. P., 1970, Histamine, in: Handbook of Neurochemistry, Volume 4 ( A. Lajtha, ed.), Plenum Press, New York, pp. 221–250.Google Scholar
  29. Green, J. P., 1983, Histamine receptors in brain, in: Handbook of Psychopharmacology, Volume 17 ( L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds.), Plenum Press, New York, pp. 385–419.Google Scholar
  30. Green, J. P., and Maayani, S., 1977, Tricyclic antidepressant drugs block histamine H2-receptors in brain, Nature. 269: 163–165.PubMedCrossRefGoogle Scholar
  31. Green, J. P., Johnson, C. L., and Weinstein, H., 1978, Histamine as a neurotransmitter, in: Psychopharmacology: A Generation of Progress ( A. Lipton, A. Di Mascio, and K. F. Killam, eds.), Raven Press, New York, pp. 319–332.Google Scholar
  32. Green, M. D., Cox, B., and Lomax, P., 1976, Sites and mechanisms of action of histamine in the central thermoregulatory pathways of the rat, Neuropharmacology. 15: 321–324.PubMedCrossRefGoogle Scholar
  33. Gross, P. M., 1982, Cerebral histamine: indications for neuronal and vascular regulation, J. Cereb. Blood Flow Metab. 2: 3–23.PubMedCrossRefGoogle Scholar
  34. Gruol, D. L., and Weinreich, D., 1979, Two pharmacologically distinct histamine receptors mediating membrane hyperpolarization on identified neurons of aplysia californica, Brain Res. 162: 281–301.PubMedCrossRefGoogle Scholar
  35. Grzanna, R., and Shultz, L. D., 1982, The contribution of mast cells to the histamine content of the central nervous system: A regional analysis, Life Sci. 30: 1959–1964.PubMedCrossRefGoogle Scholar
  36. Haas, H. L., 1974, Histamine: Action on single hypothalamic neurones, Brain Res. 76: 363–366.PubMedCrossRefGoogle Scholar
  37. Haas, H. L., 1981, Histamine hyperpolarizes hippocampal neurones in vitro, Neurosci. Lett. 22: 75–78.PubMedCrossRefGoogle Scholar
  38. Haas, H. L., 1984, Histamine potentiates neuronal excitation by blocking a calcium dependent potassium conductance, Agents Actions. 14: 534–537.PubMedCrossRefGoogle Scholar
  39. Haas, H. L., 1985, Histamine may act through cyclic AMP on hippocampal neurones, Agents Actions. 16: 234–235.PubMedCrossRefGoogle Scholar
  40. Haas, H. L., and Bucher, U. M., 1975, Histamine H2-receptors on single central neurones, Nature. 255: 634–635.PubMedCrossRefGoogle Scholar
  41. Haas, H. L., and Geller, H. M., 1982, Electrophysiology of histaminergic transmission in the brain, in: Advances in Histamine Research, Advances in the Biosciences, Volume 33, ( B. Urnäs and K. Tasaka, eds.) Pergamon Press, Oxford, pp. 81–91.Google Scholar
  42. Haas, H. L., and Konnerth, A., 1983, Histamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells, Nature. 302: 432–434.PubMedCrossRefGoogle Scholar
  43. Haas, H. L., and Wolf, P., 1977, Central actions of histamine, microelectrophoretic studies, Brain Res. 122: 269–279.PubMedCrossRefGoogle Scholar
  44. Haas, H. L., Anderson, E. G., and Hösli, L., 1973, Histamine and metabolites: Their effects and interactions with convulsants on brain stem neurones, Brain Res. 51: 269–278.PubMedCrossRefGoogle Scholar
  45. Haas, H. L., Wolf, P., and Nussbaumer, J. -C., 1975, Histamine: Action on supraoptic and other hypothalamic neurones in the cat, Brain Res. 88: 166–170.PubMedCrossRefGoogle Scholar
  46. Haas, H. L., Wolf, P., Palacios, J. M., Garbarg, M., Barbin, G., and Schwartz, J. C., 1978, Hypersensitivity to histamine in the guinea-pig brain: Microiontophoretic and biochemical studies, Brain Res. 156: 275–291.PubMedCrossRefGoogle Scholar
  47. Haas, H. L., Jefferys, J. G. R., Slater, N. T., and Carpenterr, D. O. 1984, Modulation of low calcium-induced field bursts in the hippocampus by monoamines and cholinominetics, Pflügers Arch. 400: 28–33.PubMedCrossRefGoogle Scholar
  48. Hill, S. J., Young, J. M., and Marrian, D. H., 1978, Specific binding of 3H-mepyramine to histamine H1-receptors in intestinal smooth muscle, Nature. 270: 361–363.CrossRefGoogle Scholar
  49. Kanof, P. D., and Greengard, P., 1979, Pharmacological properties of histamine sensitive adenylate cyclase from mammalian brain, J. Pharmacol. Exp. Ther. 209: 87–96.PubMedGoogle Scholar
  50. Kwiatkowski, H., 1943, Histamine in nervous tissue, J. Physiol. (Lond.) 102: 32–41.Google Scholar
  51. Lakoski, J. M., Gallagher, D. W., and Aghajanian, G. K., 1984, Histamine-induced depression of serotonergic dorsal raphe neurons: Antagonism by cimetidine, a reevaluation, Eur. J. Pharmacol. 103: 153–156.PubMedCrossRefGoogle Scholar
  52. Lancaster, B., and Adams, P. R., 1984, Single electrode voltage clamp of the slow AHP current in rat hippocampal pyramidal cells, Neurosci. Abstr. 10: 872.Google Scholar
  53. Lindl, T., 1978, Cyclic AMP and its relation to ganglionic transmission. A combined biochemical and electrophysiological study of the rat superior cervical ganglion in vitro, Neuropharmacology. 18: 227–235.CrossRefGoogle Scholar
  54. Lipinski, J. F., Schaumburg, H. H., and Baldessarini, R. J., 1973, Regional distribution of histamine in human brain, Brain Res. 52: 403–408.PubMedCrossRefGoogle Scholar
  55. Madison, D. V., and Nicoll, R. A., 1984, Control of the repetitive discharge of Ca 1 pyramidal neurones in vitro, J. Physiol. (Lund.) 354: 319–331.Google Scholar
  56. McCaman, R. E., and Weinreich, D., 1982, On the nature of histamine-mediated slow hyper-polarizing synaptic potentials in identified molluscan neurones, J. Physiol. (Land.) 328: 485–506.Google Scholar
  57. Norris, D. B., Gajtkowski, G. A., and Rising, T. J., 1984, Histamine Hz-binding studies in the guinea pig brain, Agents Actions. 14: 543–545.PubMedCrossRefGoogle Scholar
  58. Palacios, J. M., Garbarg, M., Barbin, G., and Schwartz, J. C., 1978, Pharmacological characterization of histamine receptors mediating the stimulation of cyclic AMP accumulation in slices from guinea pig hippocampus, Mol. Pharmacol. 14: 971–982.PubMedGoogle Scholar
  59. Palacios, J. M., Wamsley, J. K., and Kuhar, M. J., 1981, The distribution of histamine H1-receptors in the rat brain: An autoradiographic study, Neuroscience. 6: 15–37.PubMedCrossRefGoogle Scholar
  60. Panula, P., Yang, H. -Y. T., and Costa, E., 1984, Histamine containing neurones in the rat hypothalamus, Proc. Natl. Acad. Sci. USA. 81: 2572–2576.PubMedCrossRefGoogle Scholar
  61. Phillis, J. W., Tebecis, A. K., and York, D. H., 1968a, Depression of spinal motoneurones by noradrenaline, 5-hydroxytryptamine and histamine, Eur. J. Pharmacol. 4: 471–475.PubMedCrossRefGoogle Scholar
  62. Phillis, J. W., Tebecis, A. K., and York, D. H., 1968b, Histamine and some antihistamines: their actions on cerebral cortical neurones, Br. J. Pharmacol. 33: 426–440.Google Scholar
  63. Phillis, J. W., Kostopoulos, G. K., and Odutola, A., 1975, On the specificity of histamine H2-receptor antagonists in the rat cerebral cortex, Can. J. Physiol. Pharmacol. 53: 1205–1209.PubMedCrossRefGoogle Scholar
  64. Pollard, H., Bischoff, S., and Schwartz, J. C., 1974, Turnover of histamine in rat brain and its decrease under barbiturate anesthesia, J. Pharmacol. Exp. Ther. 190: 88–99.PubMedGoogle Scholar
  65. Renaud, L. P., 1976, Histamine microiontophoresis on identified hypothalamic neurons: 3-Patterns of response in the ventromedial nucleus of the rat, Brain Res. 115: 339–344.PubMedCrossRefGoogle Scholar
  66. Roberts, F., and Calcutt, C. R., 1983, Histamine and the hypothalamus, Neuroscience. 9: 721–739.PubMedCrossRefGoogle Scholar
  67. Sastry, B. S. R., and Phillis, J. W., 1976a, Depression of rat cerebral cortical neurones by H1 and H2 histamine receptors agonists, Eur. J. Pharmacol. 38: 269–273.PubMedCrossRefGoogle Scholar
  68. Sastry, B. S. R., and Phillis, J. W., 1976b, Evidence for an ascending inhibitory histaminergic pathway to the cerebral cortex, Can. J. Physiol. Pharmacol. 54: 782–786.PubMedCrossRefGoogle Scholar
  69. Satayavivad, U., and Kirsten, E., 1977, Iontophoretic studies of histamine and histamine antagonists in the feline vestibular nuclei, Eur. J. Pharmacol. 41: 17–26.PubMedCrossRefGoogle Scholar
  70. Schwartz, J. C., 1975, Histamine as a transmitter in brain, Life Sci. 17: 503–518.PubMedCrossRefGoogle Scholar
  71. Schwartz, J. C., 1979, Histamine receptors in brain, Life Sci. 25: 895–912.PubMedCrossRefGoogle Scholar
  72. Schwartz, J. C., Garbarg, M., and Quach, T. T., 1981, Histamine receptors as targets for tricyclic antidepressants, Trends Pharmacol. Sci. 2: 122–125.CrossRefGoogle Scholar
  73. Schwartz, J. C., Garbarg, M., and Pollard, H., 1985, Histaminergic transmission in brain, Handbook of Physiology, American Physiological Society, in press.Google Scholar
  74. Segal, M., 1980, Histamine produces a calcium-sensitive depolarization of hippocampal pyramidal cells in vitro, Neurosci. Lett. 19: 67.PubMedCrossRefGoogle Scholar
  75. Segal, M., 1981, Histamine modulates reactivity of hippocampal CA 3 neurons to afferent stimulation in vitro, Brain Res. 213: 443–448.PubMedCrossRefGoogle Scholar
  76. Snyder, S. H., and Taylor, K. M., 1972, Histamine in the brain: A neurotransmitter, in: Perspectives in Neuropharmacology (S. H. Snyder, ed.), Oxford University Press, New York, pp. 43–73.Google Scholar
  77. Steinbusch, H. W. M., and Mulder, A. H., 1984, Immunohistochemical localization of histamine in neurons and mast cells in the rat brain, in: Handbook of Chemical Neuroanatomy, Vol. 3 ( A. Björklund, T. Hökfelt, and M. J. Kuhar, eds.), Elsevier, Amsterdam, pp. 126–140.Google Scholar
  78. Study, R. E., and Greengard, P., 1978, Regulation by histamine of cyclic mucleotide levels in sympathetic ganglia, J. Pharmacol. Exp. Ther. 207: 767–778.PubMedGoogle Scholar
  79. Sweatman, P., and Jell, R. M., 1977, Dopamine and histamine sensitivity of rostral hypothalamic neurones in the cat: Possible involvement in thermoregulation, Brain Res. 127: 173–178.PubMedCrossRefGoogle Scholar
  80. Tran, V. T., Lebovitz, R., Toll, L., and Snyder, S. H., 1981, [3H]Doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates, Eur. J. Pharmacol. 70: 501–509.Google Scholar
  81. Turner, J. D., and Cottrell, G. A., 1977, Properties of an identified histamine containing neurone, Nature. 267: 447–448.PubMedCrossRefGoogle Scholar
  82. Watanabe, T., Taguchi, Y., Hayashi, H., Tanaka, J., Shiosaka, S., Tohyama, M., Kubota, H., Terano, Y., and Wada, H. (1983). Evidence for the presence of a histaminergic neuron system in the rat brain: An immunohistochemical analysis, Neurosci. Lett. 39: 249–254.PubMedCrossRefGoogle Scholar
  83. Weiner, R. I., and Ganong, W. F., 1978, Role of brain monoamines and histamine in regulation of anterior pituitary secretion, Physiol. Rev. 58: 905–976.PubMedGoogle Scholar
  84. Weinreich, D., 1977, Histamine containing neurons in Aplysia, in: Biochemistry of Characterized Neurons ( C. N. N. Osborne, ed.), Pergamon Press, Oxford, pp. 153–175.Google Scholar
  85. Wilcox, B. J., and Seybold, V. S., 1982, Localization of neuronal histamine in rat brain, Neurosci. Lett. 29: 105–110.PubMedCrossRefGoogle Scholar
  86. Wolf, P., and Monnier, M., 1973, Electroencephalographic, behavioral and visceral effects of intraventricular infusion of histamine in the rabbit, Agents Actions. 3: 196.PubMedCrossRefGoogle Scholar
  87. Yamatodani, A., Maeyama, K., Watanabe, T., Wada, H., and Kitamura, Y., 1982, Tissue distribution of histamine in a mutant mouse deficient in mast cells. Clear evidence for the presence of non mast cell histamine, Biochem. Pharmacol. 31: 305–310.PubMedCrossRefGoogle Scholar

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© Plenum Press, New York 1985

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  • Helmut L. Haas

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