Agents and Actions

, Volume 12, Issue 4, pp 425–430 | Cite as

The effects of cimetidine on histamine atrial chronotropic receptor activity

  • M. J. Hughes
Histamine and Kinins


Clinically useful histamine antagonists have been reported to be specific for H1-or H2-receptors. However, data is accumulating that the specificity of those agents may be relative. This study was undertaken in an attempt to calrify this point.

Histamine stimulates the chronotropic responses of rabbit atria by acting on both H1- and H2-receptors. Cimetidine (H2-antagonist) and diphenhydramine (H1-antagonist) both cause some inhibition of the histamine response, but there is no evidence of competitive blockade with these antagonists given separately or in combination. 4-Methylhistamine (H2-agonist) stimulates chronotropic activity, and both H1-and H2-antagonists reduce this response to some degree. 2-Methylhistamine (H1-agonist) is a less effective agonist (perhaps rabbit atria contain fewer H1-receptors), but the response is also decreased by either H1-or H2-antagonists. These two ‘specific’ agonists were combined to stimulate the histamine responses, and the antagonists were given simultaneously. The results were qualitatively similar to those obtained with histamine. The question remains: (1) are these agonists and antagonists specific or (2) are the rabbit atrial chronotropic receptors not typical of the H1-and H2-type receptor?


Histamine Cimetidine Receptor Activity Diphenhydramine Chronotropic Response 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    J.W. Black, W.A.M. Duncan, C.J. Durant, C.R. Ganellin andM.E. Parsons,Definition and antagonism of histamine H 2-receptors, Nature236, 385–390 (1972).PubMedGoogle Scholar
  2. [2]
    J.W. Black, W.A.M. Duncan, J.C. Emmett, C.R. Ganellin, T. Hesselbo, M.E. Parsons andJ.H. Wylie,Metiamide-an orally active histamine H 2-receptor antagonist, Agents and Actions3, 133–137 (1973).PubMedGoogle Scholar
  3. [3]
    R.W. Brimblecombe, W.A.M. Duncan, G.J. Durant, J.C. Emmett, C.R. Ganellin andM.E. Parsons,Cimetidine-A non-thiourea H 2-receptor antagonist, J. Inter. Med. Res.3, 86–92 (1975).Google Scholar
  4. [4]
    S.A.M., Cross,Localization of histamine and histamine H 2-receptor antagonists in the gastric mucosa, Histochem. J.9, 619–744 (1977).CrossRefPubMedGoogle Scholar
  5. [5]
    S.R. Lee andC. Tasman-Jones,Prevention of acute gastric ulceration in the rat by cimetidine, a histamine H 2-receptor antagonist, Clin. Exp. Pharmac. Physiol.51, 61–66 (1978).Google Scholar
  6. [6]
    S. Maslinski andK.-Fr. Sewing,Effect of cimetidine on gastric mucosal histamine and histidine decarboxylase activity in rats, Digestion15, 121–128 (1977).PubMedGoogle Scholar
  7. [7]
    S. Okabe, K. Takeuchi, T. Murata andT. Urushidani,Effects of cimetidine on healing of chronic gastric and duodenal ulcers in dogs, Am. J. Digest. Dis.23, 166–168 (1978).CrossRefPubMedGoogle Scholar
  8. [8]
    D. Reinhardt, U. Schmidt, O.E. Brodde andH.J. Schuemann,H 1-and H 2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscle from guinea-pig hearts, Agents and Actions7, 1–12 (1977).Google Scholar
  9. [9]
    C.L. Johnson, H. Weinstein andJ.P. Green,Studies on histamine H 2-receptors coupled to cardiac adenylate cyclase, Mol. Pharmac.16, 417–428 (1979).Google Scholar
  10. [10]
    C.L. Johnson, H. Weinstein andJ.P. Green,Studies on histamine H 2-receptors coupled to cardiac adenylate cyclase, Biochem. et Biophys. Acta587, 155–168 (1979).Google Scholar
  11. [11]
    G. Bertoccini, G. Coruzzi andT. Vitali,Effect of histamine and related compounds on the papillary muscle of the guinea pig, Pharmac. Res. Comm.10, 747–757 (1978)Google Scholar
  12. [12]
    K. Shigenobu, H. Tatsuno, N. Matsuki, T. Oshima andY. Kasuya,Electrophysiological and mechanical studies on the cardiac effects of a histamine H 2-receptor agonist, cimetidine, in the isolated guinea pig myocardium, J. Pharmac Dyn.2, 141–150 (1979).Google Scholar
  13. [13]
    J.H. Zavecy andR. Levi,Histamine-induced negative inotropism: mediated by H 1-receptors, J. Pharmac. Ther.206, 274–280 (1978).Google Scholar
  14. [14]
    R. Levi andJ.H. Zavecy Acceleration of idioventricular rhythms by histamine in guinea pig heart, Circ. Res.44, 847–855 (1979).PubMedGoogle Scholar
  15. [15]
    E.I. Laher andJ.H. McNeill,Histamine responses in cat heart, Proc. West Pharmac. Sco.22, 419–421 (1979).Google Scholar
  16. [16]
    G.R. Hageman, F. Urthaler, J.H. Isobe andT.N. James,Chronotropic and dromotropic effects of histamine on the canine heart, Chest75, 597–604 (1979).PubMedGoogle Scholar
  17. [17]
    D.A.A. Owen,Histamine receptors in the cardiovascular system, Gen. Pharmac.8, 141–156.Google Scholar
  18. [18]
    M.J. Hughes andR. Lydic, Characteristics of H1 and H2 histamine receptors which mediate the chronotropic response of rabbit atrial muscle. In:Histamine Receptors: A Richards Symposium, pp. 143–159. (Ed. T.O. Yellin). S. P. Medical and Scientific Books, Jamaica, N.YY. 1979.Google Scholar
  19. [19]
    M.J. Hughes andI.A Coret,On specificity of histamine receptors in the heart, Am. J. Physiol.223, 1257–1262 (1972).PubMedGoogle Scholar
  20. [20]
    I.A. Coret A quantitative description of chronotropic effects of histamine on rabbit heart, Arch. Inter. Pharmac. Ther.208, 117–137 (1974).Google Scholar
  21. [21]
    K.E. Light andM.J. Hughes,Liberation of histamine by compound 48/80, tolazoline, betahistine and burimamide from isolated spontaneously beating guinea pig rabbit atrial pairs, Agents and Actions9, 141–149 (1979).PubMedGoogle Scholar
  22. [22]
    D.A. Cook, T.P. Kenakin andC.A. Krueger,Alterations in temperature and histamine receptor function, Fedn Proc.36, 2584–2589 (1977).Google Scholar

Copyright information

© Birkhäuser Verlag 1982

Authors and Affiliations

  • M. J. Hughes
    • 1
  1. 1.Department of PhysiologyTexas Technical University Health Sciences CenterLubbockUSA

Personalised recommendations