The H89 cAMP-dependent protein kinase inhibitor blocks Plasmodium falciparum development in infected erythrocytes

In Plasmodium falciparum, the causative agent of human malaria, the catalyt ic subunit gene of cAMP-dependent protein kinase (Pfpka-c) exists as a sing le copy. Interestingly, its expression appears developmentally regulated, b eing at higher levels in the pathogenic asexual stages than in the sexual f orms of parasite that are responsible for transmission to the mosquito vect or. Within asexual parasites, PfPKA activity can be readily detected in sch izonts. Similar to endogenous PKA activity of noninfected red blood cells, the parasite enzyme can be stimulated by cAMP and inhibited by protein kina se inhibitor. Importantly, ex vivo treatment of infected erythrocytes with the classical PKA-C inhibitor H89 leads to a block in parasite growth. This suggests that the PKA activities of infected red blood cells are essential for parasite multiplication. Finally, structural considerations suggest th at drugs targeting the parasite, rather than the erythrocyte enzyme, might be developed that could help in the fight against malaria.