ALTERATIONS IN G-PROTEIN-REGULATED TRANSMEMBRANE SIGNALING INDUCED INMURINE MYOCARDIUM BY COXSACKIEVIRUS B3 INFECTION

Objective: Cardiomyopathy is usually;associated with marked alteration s in myocardial transmembrane signalling. Although acute viral myocard itis may result in chronic cardiomyopathy in some cases, the possible consequences of viral infection on function of the myocardial signal-t ransducing complex have not been explored. Therefore, the present stud y was designed to investigated the G-protein-regulated adenylyl cyclas e signalling system in murine myocardium during myocarditis induced by coxsackievirus B3 (CVB3) infection. Methods: We examined the function al characteristics of adenylyl cyclase as well as the function and dis tribution of beta-adrenoceptors, m-cholinoceptors and G-proteins in my ocardial plasma membranes isolated from the hearts of mice with acute (7 days pi) or late phase (21 days pi) myocarditis and the obtained re sults were compared with the corresponding data determined in age-matc hed controls. Results: While the basal adenylyl cyclase activity was n ot significantly altered, the ability of forskolin, sodium fluoride an d GTP gamma S to activate adenylyl cyclase was lowered by about 20% in samples from virus-infected animals. The level of G(s alpha) in myoca rdial plasma membranes as well as the functional activity of G(s alpha ) was not affected by viral infection, but the G(i alpha) content was increased by about 20%. The total number of beta-adrenoceptors in myoc ardial plasma membranes increased by about 12-15% due to higher conten t of the beta(2)-adrenoceptor subtype. Although the agonist-binding pa rameters of P-adrenoceptors were not significantly altered, the abilit y of these receptors to mediate stimulation of adenylate cyclase was m arkedly diminished (by 56-80%). The total number of m-cholinoceptors i n samples derived from virus-infected mice increased considerably (by 29-59%) and a significant proportion of the receptors shifted to a hig her affinity status, but their ability to transduce agonist signals wa s impaired. Conclusions: These data are the first to demonstrate that several different sites of the myocardial G-protein-regulated adenylyl cyclase sil:nalling complex are significantly altered in acute as wel l as in late phase of CVB3-induced myocarditis.