INCREASES IN CYCLIC-AMP LEVELS COUPLE TO H1 RECEPTORS IN ATRIA FROM AUTOIMMUNE MYOCARDITIS MICE

We have previously shown that myocardium from experimental autoimmune myo carditis 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 cont rol mice. Addition of mepyramine before ThEA caused cyclic AMP levels to fall to a level similar to basal, confirming the H1 receptor partic ipation. Histamine at low concentrations mimicked the ThEA action on H 1 receptor-stimulation of cyclic AMP production by autoimmune myocardi um. 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, genera ting some oxidative metabolites (1P3-DAG), which in turn may be respon sible 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 b oth pathways are implicated in this effect. Data shows that the stimul ation of H1 receptors by specific agonist in atria from autoimmune myo carditis mice, augments the cyclic AMP, requiring the hydrolysis of ph osphioinositide cycle. The role of this cyclic AMP augmentation in myo cardium from autoimmune myocarditis mice, will provide a basis to asse ss the role of this second messenger as an important factor in the reg ulation and/or modulation of the physiological behaviour of the heart in the course of autoimmune myocarditis.