title: Increases in cyclic AMP levels couple to H1 receptors in atria from autoimmune myocarditis mice.
abstract: We have previously shown that myocardium from experimental autoimmune myocarditis expresses H1 receptors not present in normal mice heart. ThEA acting via H1 receptors, augments cyclic AMP production in atria from autoimmune myocarditis mice without any effect on atria from control mice. Addition of mepyramine before ThEA caused cyclic AMP levels to fall to a level similar to basal, confirming the H1 receptor participation. Histamine at low concentrations mimicked the ThEA action on H1 receptor-stimulation of cyclic AMP production by autoimmune myocardium. The fact that the inhibition of phospholipase C blocked the cyclic AMP stimulation by ThEA, supports the assumption that this action is secondary to receptor-mediated hydrolysis of phosphoinositides, generating some oxidative metabolites (IP3-DAG), which in turn may be responsible for the cyclic AMP effect. So, the inhibition of protein kinase C and calcium/calmodulin partially prevented the stimulatory action of ThEA on cyclic AMP levels in autoimmune myocardium, suggesting that both pathways are implicated in this effect. Data shows that the stimulation of H1 receptors by specific agonist in atria from autoimmune myocarditis mice, augments the cyclic AMP, requiring the hydrolysis of phosphoinositide cycle. The role of this cyclic AMP augmentation in myocardium from autoimmune myocarditis mice, will provide a basis to assess the role of this second messenger as an important factor in the regulation and/or modulation of the physiological behaviour of the heart in the course of autoimmune myocarditis.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Goren
authors.forename: L
authors.initials: L
authors.lastname: Sterin-Borda
authors.forename: C P
authors.initials: CP
authors.lastname: Leiros
authors.forename: E S
authors.initials: ES
authors.lastname: Borda
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000502:physiology; D006325:Heart Atria / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D017442:Histamine Agonists; D006633:Histamine Antagonists; D010716:Phosphatidylinositols; D011969:Receptors, Histamine H1; D013844:Thiazoles; C029345:2-(2-aminoethyl)thiazole; D002927:Cimetidine; D006632:Histamine; D000242:Cyclic AMP; D011738:Pyrilamine