Effect of histamine in autoimmune myocarditis mice.
The contractile effect of histamine, as well as the H1 receptor population and H2 receptor-mediated cAMP production, were measured in cardiac tissue from control normal and autoimmune myocarditis mice. Histamine triggered positive chronotropy and negative inotropy at high concentrations in both control and autoimmune auricles, H2 receptors being the most important mediator of these responses. In contrast, in atria from autoimmune myocarditis mice, histamine at lower concentrations caused positive inotropy and negative chronotropy. These effects, not verified in the normal control atria, are mediated by H1 receptors. The expression of H2 and H1 receptors mediating the cardiac response to histamine was evaluated through histamine-stimulated cAMP level and binding of [3H] mephyramine, respectively. Both control and autoimmune myocardium were able to increase cAMP levels, an effect that was inhibited by H2 antagonist drug. The amount of cAMP was significantly higher in control myocardium than in those from autoimmune ones. Saturable binding of [3H] mephyramine occurs in autoimmune myocardium, with distinct high and low affinity binding sites. In control myocardium non-saturable binding was detected. These results suggest that H1 and H2 receptors coexist in heart from autoimmune myocarditis mice, whereas only H2 receptors are present in myocardium from control mice. The presence of H1 receptors in autoimmune myocardium could be an important factor in the regulation of its physiological behaviour.
Goren
N
N
Centro de Estudios Farmacologicos y Botanicos (CEFYBO), Buenos Aires, Argentina.
Perez Leiros
C
C
Sterin-Borda
L
L
Borda
E
E
D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology*; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009205:Myocarditis / Q000503:physiopathology*; D011738:Pyrilamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology
D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D000242:Cyclic AMP; D011738:Pyrilamine