Erythrocytic mechanisms involved in malarial infection are poorly understood. We have found that signaling via the erythrocyte β2-adrenergic receptor and heterotrimeric guanine nucleotide-binding protein (Gαs) regulated the entry of the human malaria parasite Plasmodium falciparum. Agonists that stimulate cyclic adenosine 3′,5′-monophosphate production led to an increase in malarial infection that could be blocked by specific receptor antagonists. Moreover, peptides designed to inhibit Gαs protein function reduced parasitemia in P. falciparum cultures in vitro, and β-antagonists reduced parasitemia of P. berghei infections in an in vivo mouse model. Thus, signaling via the erythrocyte β2-adrenergic receptor and Gαs may regulate malarial infection across parasite species.
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