title: Endothelin and bradykinin: 'brothers-in-arms' in Chagas vasculopathies?
abstract: Reports of Chagas disease are increasing in non-endemic populations across the globe. Apart from vector eradication and prevention efforts by public health organizations, current pharmacological interventions are sparse and show important side effects. In this issue of the BJP, Andrade et al. elegantly demonstrate a new pharmacological paradigm whereby Trypanosoma cruzi host cell invasion requires significant cross-talk between receptors for kinins and endothelins. It is shown, for example, that acting via both ET(A) and ET(B) receptors, endothelin-1 (ET-1) cooperates with the (TLR2/CXCR2/B(2) kinin receptor) complex to activate inflammatory processes in response to invading trypomastigotes. This study by Andrade et al. prompts, however, several important questions, summarized in this Commentary, such as the putative role of chymase-dependent production of ET-1, the contentious protective role of ACE inhibitors in Chagasic patients, the unexplored role of de novo formed B(1) receptors for kinins triggered by cytokines and the putative role of compartmentalized calcium pools in host cell invasion by trypomastigotes.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Québec, Canada. labpdj@usherbrooke.ca
authors.forename: Pedro
authors.initials: P
authors.lastname: D'Orléans-Juste
authors.forename: Ghassan
authors.initials: G
authors.lastname: Bkaily
authors.forename: Giles Alexander
authors.initials: GA
authors.lastname: Rae
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000378:metabolism*
chemical_list: D043782:Receptor, Bradykinin B2; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B