Differences in basal and stimulated cyclic AMP content in calvaria bones from normal mice and mice with an impaired lysosomal function (beige mice).

Abstract

Earlier we have shown that bone resorption is impaired in cultured calvaria from beige mice (an animal equivalent of the Chediak-Higashi syndrome in man). In the present study we have compared the concentrations of cyclic AMP and cyclic GMP in calvarial bones from beige mice with the nucleotide concentrations in bones from corresponding normal mice. In six independent experiments the basal concentrations of cyclic AMP was significantly (P less than 0.01) higher in bones from beige mice (on an average 50% augmented). The ratio of cyclic AMP/cyclic GMP was 2.43 times higher (P less than 0.01) in bones from beige mice. After stimulation with the phosphodiesterase inhibitor isobutylmethylxanthine and prostaglandin E2 no significant differences of cyclic AMP concentrations between beige and control mice could be registered. The response to adenosine was significantly higher (P less than 0.005) in bones from beige mice (4.3 +/- 0.4-fold of basal cyclic AMP concentrations, mean +/- SE) compared to control mice (1.9 +/- 0.4-fold of basal, mean +/- SE). The increased basal concentration of cyclic AMP in calvaria from beige mice may be due to increased sensitivity to some agonists, such as adenosine, rather than simply being a function of cell mass.