Radioautographic Characterization of H1 and H2 Receptor Antagonists

Binding Sites in Rat Gastric Mucosal Microcirculatory System
  • Masahiko Nakamura
  • Masaya Oda
  • Kotaro Kaneko
  • Koya Honda
  • Hirokazu Komatsu
  • Masaharu Tsuchiya
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 242)


Histamine is thought to be one of the most important neuromodulators in the gastric mucosa, participating mainly in the regulation of hydrochloric acid secretion and blood flow. Pharmacological studies revealed that the action of histamine is mediated by two types of receptors: H1 and non-H1 receptors, i.e., H2 receptors. The existence of non-H1 receptors was initially revealed through evidence that certain effects of histamine, such as gastric acid secretion and cardiac chronotropism, are not antagonized by typical antihistamines.1 The important derivation of a second class of histamine antagonists2 defined this new class of receptors, the H2 receptors, as being those which are unaffected by classical H2 antihistamines like pyrilamine. The subsequent phenomenal success of this new H2 receptor antagonist, Cimetidine, in treating duodenal ulcers by suppression of acid secretion has confirmed the functional significance of histamine in the gastric mucosa.


Gastric Mucosa Parietal Cell Mucosal Blood Flow Gastric Mucosal Blood Flow Quinuclidinyl Benzilate 
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  1. 1.
    A.S.F. Ash and H.O. Shild, Receptors mediating some action of histamine,Br. J. Pharmacol. 27:427 (1966).Google Scholar
  2. 2.
    J.W. Black, W.A.M. Duncan, C.J. Durant, C.R. Ganellin and E.M. Parsons, Definition and antagonism of histamine H2 receptors. Nature 236:385 (1972).PubMedCrossRefGoogle Scholar
  3. 3.
    G.A. Charbon, H.A.A. Brouwers and A. Sala, Histamine Hp and Hj-receptors in the gastrointestinal circulation, Naunyn-Schmiedeberg,s Arch Pharmacol 312:123 (1980).CrossRefGoogle Scholar
  4. 4.
    J.G. Wood and H.W. Davenport, Measurement of canine gastric vascular permeability to plasma proteins in the normal and protein-losing states, Gastroenterology 82:725 (1982).PubMedGoogle Scholar
  5. 5.
    B.P. Curwain and N.C. Turner, The involvement of histamine receptor subtypes in gastric acid secretion and mucosal blood flow in the anesthetized rabbit, J. Physiol. (London) 311:431 (1981).Google Scholar
  6. 6.
    M. Nakamura, M. Oda, Y. Yonei, N. Tsukada, N. Watanabe, H. Komatsu and M. Tsuchiya, Demonstration of the localization of muscarinic acetylcholine receptors in the gastric mucosa — light and electron microscopic autoradiographic studies using 3H-quinuclidinyl benzilate,Acta Histochem. Cytochem. 17:297 (1984).CrossRefGoogle Scholar
  7. 7.
    M. Nakamura, M. Oda, K. Kaneko, K. H. Komatsu, T. Fujiwara, L Okazaki and M. Tsuchiya, Radioautographic demonstration of 3H-QNB, 3H-cimetidine, 3H-TZU and 125I-gastrin binding sites on the parietal cell: internalization of receptor-bound ligand, J. Electron Microsc. 35 (Suppl.):3553 (1986).Google Scholar
  8. 8.
    T. Nagata, T. Nawa and S. Yokota, A new technique for electron microscopic dry-mounting radio-autography of soluble-compounds, Histochemie 18:241 (1969).PubMedCrossRefGoogle Scholar
  9. 9.
    M.M. Salpeter, L. Bachmann and E.E. Salpeter, Resolution in electron microscope radioautography, J. Cell Biol. 41:1 (1969).PubMedCrossRefGoogle Scholar
  10. 10.
    M. Nakamura, M. Oda, Y. Yonei, N. Tsukada, H. Komatsu, K. Kaneko and M. Tsuchiya, Muscarinic acetylcholine receptors in rat gastric mucosa a radioautographic study using a potent muscarinic antagonist, 3H-pirenzepine, Histochemistry 83:479 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    D.J. Meiners, Y.G. Deshpande and D.L. Kaminski, The role of histamine in control of gastric mucosal blood flow in dogs, J. Surg. Res. 32:608 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    C. Heltianu, M. Simionescu and N. Simionescu, Histamine receptors of the microvascular endo thelium revealed in situ with a histamine-ferritin conjugate: characteristic high-affinity binding sites in venules, J. Cell Biol. 93:357 (1982).PubMedCrossRefGoogle Scholar
  13. 13.
    E.M. Renkin, R.D. Carter and W.L. Joyner, Mechanism of the sustained action of histamine and bradykinin on transport of large molecules across the capillary walls in the dog paw, Microvasc. Res. 7:49 (1974).PubMedCrossRefGoogle Scholar
  14. 14.
    G. Majno and O.E. Palade. Studies on inflammation: I. the effect of histamine and serotonin on vascular permeability: an electron microscopic study, J. Biophys. Biochem. Cytol. 11:571 (1961).PubMedCrossRefGoogle Scholar
  15. M. Nakamura, M. Oda, K. Kaneko, K. Honda, H. Komatsu and M. Tsuchiya, Radioautographic study of the binding sites of QNB on the isolated gastric glandular cell, Histochemistry (submitted).Google Scholar
  16. 16.
    M. Nakamura, M. Oda, Y. Yonei, K. Kaneko, H. Komatsu, N. Tsukada, M. Tsuchiya and Y. Fujishiro, Radioautographic demonstration of localization of histamine H, and H2 receptors in the gastric mucosa, in “Microcirculation Annual 1985. Japanese society for microcirculation,” M. Tsuchiya, M. Asano, M. Oda and I. Okazaki, ed., Excerpta Medica, pp. 217 (1985).Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Masahiko Nakamura
    • 1
  • Masaya Oda
    • 1
  • Kotaro Kaneko
    • 1
  • Koya Honda
    • 1
  • Hirokazu Komatsu
    • 1
  • Masaharu Tsuchiya
    • 1
  1. 1.Department of Internal Medicine, School of MedicineKeio UniversityTokyo 160Japan

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