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, Volume 10, Issue 5, pp 422–426 | Cite as

Binding of [3H]cimetidine to rat brain tissue

  • Ian R. Smith
  • Mark T. Cleverley
  • C. Robin Ganellin
  • Kathleen M. Metters
Histamine and Kinins

Abstract

Binding of [3H]cimetidine to rat brain tissue was investigated, and a saturable binding with dissociation constant 0.22±0.05 μM found. This binding is inhibited by a range of imidazole-derived histamine H2-receptor antagonists, but not by a number of non-imidazole H2-receptor antagonists. It is concluded that the [3H]cimetidine binding site in rat brain tissue that is labelled in these experiments is not the histamine H2-receptor.

Keywords

Binding Site Histamine Brain Tissue Cimetidine Dissociation Constant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. [1]
    M. Chasin, F. Mamrak, S.G. Samaniego andS.M. Hess,Characteristics of the Catecholamine and Histamine Receptor sites Mediating Accumulation of Cyclic Adenosiee 3′,5′-Monophosphate in Guinea-Pig Brain, J. Neurochem.21, 1415 (1973).PubMedGoogle Scholar
  2. [2]
    K. Dismukes, M. Rogers andJ.W. Daly,Cyclic Adenosine 3′,5′-Monophosphate Formation in Guinea-Pig Brain Slices: Effect of H 1-and H 2-Histaminergic Agonists, J. Neurochem.26, 785 (1976).PubMedGoogle Scholar
  3. [3]
    J.M. Palacios, M. Garbarg, G. Barbin andJ.C. Schwartz,Pharmacological Characterization of Histamine Receptors Mediating the Stimulation of Cyclic AMP Accumulation in Slices from Guinea-Pig Hippocampus, Mol. Pharmacol.14, 971 (1978).PubMedGoogle Scholar
  4. [4]
    J.P. Green, C.L. Johnson, H. Weinstein andS. Maayani,Antagonism of Histamine-Activated Adenylate Cyclase in Brain by D-Lysergic Acid Diethylamide, Proc. nat. Acad. Sci USA74, 5697 (1977).PubMedGoogle Scholar
  5. [5]
    P.D. Kanof andP. Greengard,Pharmacological Properties of Histamine-Sensitive Adenylate Cyclase from Mammalian Brain, J. Pharmac. exp. Ther.209, 87 (1979).Google Scholar
  6. [6]
    S.R. Nahorski, K.J. Rogers andB.M. Smith,Stimulation of Cyclic Adenosine 3′,5′-monophosphate in Chick Cerebral Hemisphere Slices: Effects of H 1 and H 2 Histaminergic Agonists and Antagonists, Brain Res.126, 387 (1977).CrossRefPubMedGoogle Scholar
  7. [7]
    S.J. Hill, P.C. Emson andJ.M. Young,The Binding of [3H]mepyramine to Histamine H 1-Receptors in Guinea Pig Brain, J. Neurochem.31, 997 (1978).Google Scholar
  8. [8]
    R.S.L. Chang, V.T. Tran andS.H. Snyder,Heterogeneity of Histamine H 1-Receptors: Species Variations in [3 H]mepyramine Binding of Brain Membranes, J. Neurochem.32, 1653 (1979).Google Scholar
  9. [9]
    V.T. Tran, R.S.L. Chang andS.H. Synder,Histamine H 1-Receptors Identified in Mammalian Brain Membranes with [3 H]mepyramine, Proc. nat. Acad. Sci. USA75, 6209 (1978).Google Scholar
  10. [10]
    M. Rehavt andM. Sokolovsky,Multiple Binding Sites of Tricyclic Antidepressant Drugs to Mammalian Brain Receptors, Brain Res.149, 525 (1978).CrossRefPubMedGoogle Scholar
  11. [11]
    W.P. Burkard,Histamine H 2-Receptor Binding with [3 H]metidine in Brain, Eur. J. Pharmac.50, 449 (1978).CrossRefGoogle Scholar
  12. [12]
    D.A. Kendall, J.W. Ferkany andS.J. Enna,Properties of [3 H]cimetidine Binding in Rat Brain Membrane Fractions, Life Sciences26, 1293 (1980).CrossRefPubMedGoogle Scholar
  13. [13]
    G.N. Wilkinson,Statistical Estimations in Enzyme Kinetics, Biochem. J.80, 324 (1961).PubMedGoogle Scholar
  14. [14]
    R.J. Lefkowitz, L.E. Limbird, C. Mukherjee andM.G. Caron,The β-Adrenergic Receptor and Adenylate Cyclase, Biochim. Biophys. Acta457, 1 (1976).PubMedGoogle Scholar
  15. [15]
    T.O. Yellin, S.H. Buck, D.J. Gilman, D.F. Jones andJ.M. Wardleworth,ICI 125, 211: a Potent New Antisecretory Drug Acting on Histamine H 2-Receptors, The Pharmacologist21, 266 (1979), Abstract 635.Google Scholar
  16. [16]
    J. Bradshaw, R.T. Brittain, J.W. Clitherow, M.J. Daly, D. Jack, B.J. Price andR. Stables,Ranitidine (AH 19065): a New Potent, Selective Histamine H 2-Receptor Antagonist, Br. J. Pharmac.66, 464P (1979).Google Scholar
  17. [17]
    J.P. Green andS. Maayani,Tricyclic Antidepressant Drugs Block Histamine H 2-Receptor in Brain, Nature, Lond.269, 163 (1977).Google Scholar
  18. [18]
    P.D. Kanof andP. Greengard,Brain Histamine Receptors as Targets for Antidepressant Drugs, Nature, Lond.,272, 329 (1978).Google Scholar
  19. [19]
    M.E. Parsons, D.A.A. Owen, C.R. Ganellin andG.J. Durant,Dimaprit-[S-]3(N,N-dimethylamino)-propylisothiourea] — A Highly Specific Histamine H 2-Receptor Agonist,Agents and Actions7, 31 (1977).PubMedGoogle Scholar
  20. [20]
    G.J. Durant, W.A.M. Duncan, C.R. Ganellin, M.E. Parsons, R.C. Blakemore andA.C. Rasmussen,Impromidine (SK&F 92676) is a very Potent and Specific Agonist for Histamine H 2-Receptors, Nature, Lond.276, 403 (1978).Google Scholar
  21. [21]
    S.T. Nielsen, T.O. Yellin, P.N. Edwards andM.S. Large,Radioligand Binding Assay of H 2-Receptors with [3 H]ICIA 5165, The Pharmacologist21, 265 (1979), Abstract 634.Google Scholar
  22. [22]
    C.R. Ganellin,Selectivity and the Design of Histamine H 2-Receptor Antagonists, J. appl. Chem. Biotechnol.28, 183 (1978).Google Scholar

Copyright information

© Birkhäuser Verlag 1980

Authors and Affiliations

  • Ian R. Smith
    • 1
  • Mark T. Cleverley
    • 1
  • C. Robin Ganellin
    • 1
  • Kathleen M. Metters
    • 1
  1. 1.Research InstituteSmith Kline and French Research Ltd.Welwyn Garden CityUK

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