EXPRESSION OF HISTAMINE H-1 RECEPTORS IN AUTOIMMUNE MYOCARDITIS MICE

Two populations of histaminergic H-1 receptors with distinct high and low affinity binding sites were characterized by the specific H-1 rece ptor antagonist [H-3]mepyramine in autoimmune myocardium. No saturable binding of the radiolabelled H-1, antagonist was observed in normal m yocardium. Reaction of autoimmune myocardium with specific H-1, agonis t (2-thiazolyl-ethylamine (ThEA)) triggered positive inotropy and nega tive chronotropy, which were inhibited by mepyramine. Inhibitors of ph ospholipase C and protein kinase C attenuated both the inotropic and c hronotropic effects of ThEA, suggesting the participation of phosphoin ositide hydrolysis in this phenomenon. The latter was verified by meas urement of polyphosphoinositide hydrolysis in autoimmune myocardium fo llowing the reaction of ThEA with histaminergic H-1, receptors. We con clude that functional H-1, histaminergic receptors could involve a dis tinctive mechanism operating in autoimmune myocardium as a result of c ardiac antigen immunization.