Effect of histamine H2-receptor and β-receptor blockade on histamine-, orciprenaline- and prostaglandin-stimulated frequency of the isolated guinea-pig atrium

Susskand, K.; Siess, M.; -Fr, K.. Sewing

Inflammation Research 5(5): 444-447

1975


ISSN/ISBN: 1023-3830
DOI: 10.1007/bf01972664
Accession: 061386436

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Abstract
For the oxyntic cell of the stomach the hypothesis was forwarded by Grossmann and Konturek [1] that, if one of its three receptors is blocked, the physico-chemical properties of the two others are changed in such a way that they respond less sensitively to their specific stimulation. This hypothesis was tested for the heart by studying the effect of histamine-H2-receptor- and β-receptor-blockade on the orciprenaline-, histamine-, and prostaglandin E1-stimulated frequency of the spontaneously beating isolated guinea-pig atrium. Therefore cumulative dose response curves were established for orciprenaline, histamine and prostaglandin E1 (PGE1) alone or in the presence of metiamide or pindolol. (1) The β-blocker pindolol inhibited the effect of orciprenaline in a competitive manner, without having an effect on histamine- and PGE1-stimulation. (2) The histamine H2-receptor blocker metiamide inhibited the histamine response competitively. (3) In contrast to pindolol, metiamide inhibited the PGE1-stimulated rise in atrial frequency, most obviously non- or uncompetitively. From these results it is evident that in the heart the particular inhibitors, at least at the receptor site, act rather specifically without affecting neighbouring receptors and that metiamide influences the PGE1-response in a way different from the receptor site.