Erythrocyte G protein-coupled receptor signaling in malarial infection.
Erythrocytic mechanisms involved in malarial infection are poorly understood. We have found that signaling via the erythrocyte beta2-adrenergic receptor and heterotrimeric guanine nucleotide-binding protein (Galphas) 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 Galphas protein function reduced parasitemia in P. falciparum cultures in vitro, and beta-antagonists reduced parasitemia of P. berghei infections in an in vivo mouse model. Thus, signaling via the erythrocyte beta2-adrenergic receptor and Galphas may regulate malarial infection across parasite species.
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000469:parasitology*; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D018512:Parasitemia; D010446:Peptide Fragments / Q000494:pharmacology; D010962:Plasmodium berghei / Q000502:physiology*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015398:Signal Transduction; D013237:Stereoisomerism; D014617:Vacuoles / Q000469:parasitology
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D010446:Peptide Fragments; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018343:Receptors, Adrenergic, beta-2; D018047:Receptors, Purinergic P1; D000526:Alprenolol; D011433:Propranolol; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs