Alterations in cardiac membrane beta-adrenoceptors and adenylyl cyclase due to hypochlorous acid.

Although neutrophils and eosinophils are known to produce hypochlorous acid (HOCI) at the site of cardiac injury, the exact role of this toxic oxidant on the signal transduction mechanism in the heart is not clear. In this study, the effects of HOCI on beta-adrenoceptors, G-proteins and adenylyl cyclase activity were assessed by incubating rat heart membranes with HOCl. The basal as well as forskolin-, NaF-, 5-guanylylimidodiphosphate-, and isoproterenol-stimulated adenylyl cyclase activities were depressed by incubating cardiac membranes with HOCl. While both the density and affinity of the beta1-adrenoceptors were decreased by treatment of cardiac membranes with HOCl, the characteristics of the beta2-adrenoceptors were not modified significantly. Although cholera toxin-stimulated adenylyl cyclase activity, cholera toxin-catalyzed ADP-ribosylation and stimulatory guanine nucleotide binding protein immunoreactivity were depressed by HOCl, the pertussis toxin-stimulated adenylyl cyclase activity, pertussis toxin-catalyzed ADP ribosylation and inhibitory guanine nucleotide binding protein immunoreactivity were unaltered by HOCl. The presence of L-methionine in the incubation medium prevented the HOCl-induced alterations in adenylyl cyclase activities and characteristics of beta1-adrenoceptors. These results suggest that HOCl may be one of the factors attenuating the beta-adrenoceptor linked signal transduction mechanism in conditions such as ischemic heart disease.