The effects of cimetidine on histamine atrial chronotropic receptor activity
- 18 Downloads
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?
KeywordsHistamine Cimetidine Receptor Activity Diphenhydramine Chronotropic Response
Unable to display preview. Download preview PDF.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- J.H. Zavecy andR. Levi,Histamine-induced negative inotropism: mediated by H 1-receptors, J. Pharmac. Ther.206, 274–280 (1978).Google Scholar
- E.I. Laher andJ.H. McNeill,Histamine responses in cat heart, Proc. West Pharmac. Sco.22, 419–421 (1979).Google Scholar
- D.A.A. Owen,Histamine receptors in the cardiovascular system, Gen. Pharmac.8, 141–156.Google Scholar
- 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
- I.A. Coret A quantitative description of chronotropic effects of histamine on rabbit heart, Arch. Inter. Pharmac. Ther.208, 117–137 (1974).Google Scholar
- D.A. Cook, T.P. Kenakin andC.A. Krueger,Alterations in temperature and histamine receptor function, Fedn Proc.36, 2584–2589 (1977).Google Scholar