ADENYLYL-CYCLASE ACTIVITY IN CLONALLY DERIVED HUMAN MYOBLAST CULTURES- EVIDENCE FOR MYOBLAST HETEROGENEITY

In vitro myogenesis recapitulates the programme of myogenesis in vivo. During the process of muscle differentiation, cAMP plays an important role in the control of gene expression and in the integration of meta bolic functions. cAMP generation may be affected by drugs or hormones that interact with the membrane-bound enzyme adenylyl cyclase, includi ng adrenergic agents and glucocorticoids. In this study, adenylyl cycl ase activity was evaluated in membranes prepared from human clonally d erived muscle cultures. In control cultures, there was considerable in ter-clonal variation in basal, sodium-fluoride and forskolin-stimulate d adenylyl cyclase activity. Cultures differed in their response to st eroids: adenylyl cyclase activity was markedly enhanced in some clones , and was significantly inhibited in other clones. Pretreatment of cul tures with pertussis toxin indicated that the effects of steroids are mediated in part by modulation of G-protein activity. These findings i ndicate a substantial heterogeneity among myoblast clones with respect to the modulating effect of steroids on adenylyl cyclase activity. Th is observation may account for the conflicting reports of steroid effe cts on muscle in vitro, and may be of relevance to the understanding o f possible transmembrane signalling alterations in muscle disease.