Cyclic AMP and adenylate cyclase activators stimulate Trypanosoma cruzi differentiation.
A chemically defined in vitro differentiating condition was used to study the potential role of cyclic AMP (cAMP) and adenylate cyclase activators on the transformation of Trypanosoma cruzi epimastigotes to the infective metacyclic trypomastigotes (metacyclogenesis). It was observed that both addition of cAMP analogs or adenylate cyclase activators to the differentiating medium stimulated the transformation of epimastigotes to metacyclic trypomastigotes. These results were further corroborated by showing that inhibitors of cAMP phosphodiesterase were stimulatory while activators of this enzyme inhibited the metacyclogenesis process. On the other hand, inhibitors of calmodulin inhibited the transformation of epimastigotes to metacyclic trypomastigotes, suggesting that T. cruzi adenylate cyclase might be activated by calmodulin. In addition, the results strongly suggest that guanine nucleotide binding proteins are involved in T. cruzi adenylate cyclase activation. This system may be useful for studying cell differentiation mechanisms in eukaryotes.
Gonzales-Perdomo
M
M
Departamento de Bioquímica e Biologia Molecular, Rio de Janeiro, Brasil.
Romero
P
P
Goldenberg
S
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002147:Calmodulin / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D003470:Culture Media; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*
D002147:Calmodulin; D003470:Culture Media; D006165:Guanylyl Imidodiphosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D000241:Adenosine; D004837:Epinephrine