Publication Date:
2003-09-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harrison, Travis -- Samuel, Benjamin U -- Akompong, Thomas -- Hamm, Heidi -- Mohandas, Narla -- Lomasney, Jon W -- Haldar, Kasturi -- AI39071/AI/NIAID NIH HHS/ -- DK32094/DK/NIDDK NIH HHS/ -- EY06062/EY/NEI NIH HHS/ -- EY10291/EY/NEI NIH HHS/ -- HL03961/HL/NHLBI NIH HHS/ -- HL55591/HL/NHLBI NIH HHS/ -- HL69630/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 19;301(5640):1734-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 Chicago Avenue, Chicago, IL 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14500986" target="_blank"〉PubMed〈/a〉
Keywords:
Adrenergic beta-2 Receptor Agonists
;
Adrenergic beta-2 Receptor Antagonists
;
Adrenergic beta-Agonists/pharmacology
;
Adrenergic beta-Antagonists/pharmacology
;
Alprenolol/pharmacology
;
Animals
;
Catecholamines/metabolism
;
Cyclic AMP/metabolism
;
Erythrocyte Membrane/metabolism
;
Erythrocytes/metabolism/*parasitology
;
GTP-Binding Protein alpha Subunits, Gs/chemistry/*metabolism
;
Humans
;
Malaria/metabolism/*parasitology
;
Membrane Microdomains/metabolism
;
Mice
;
Parasitemia
;
Peptide Fragments/pharmacology
;
Plasmodium berghei/*physiology
;
Plasmodium falciparum/growth & development/*physiology
;
Propranolol/pharmacology
;
Purinergic P1 Receptor Agonists
;
Purinergic P1 Receptor Antagonists
;
Receptors, Adrenergic, beta-2/*metabolism
;
Receptors, Purinergic P1/metabolism
;
Signal Transduction
;
Stereoisomerism
;
Vacuoles/parasitology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
