title: Non-canonical signalling and roles of the vasoactive peptides angiotensins and kinins.
abstract: GPCRs (G-protein-coupled receptors) are among the most important targets for drug discovery due to their ubiquitous expression and participation in cellular events under both healthy and disease conditions. These receptors can be activated by a plethora of ligands, such as ions, odorants, small ligands and peptides, including angiotensins and kinins, which are vasoactive peptides that are classically involved in the pathophysiology of cardiovascular events. These peptides and their corresponding GPCRs have been reported to play roles in other systems and under pathophysiological conditions, such as cancer, central nervous system disorders, metabolic dysfunction and bone resorption. More recently, new mechanisms have been described for the functional regulation of GPCRs, including the transactivation of other signal transduction receptors and the activation of G-protein-independent pathways. The existence of such alternative mechanisms for signal transduction and the discovery of agonists that can preferentially trigger one signalling pathway over other pathways (called biased agonists) have opened new perspectives for the discovery and development of drugs with a higher specificity of action and, therefore, fewer side effects. The present review summarizes the current knowledge on the non-canonical signalling and roles of angiotensins and kinins.
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Costa-Neto
authors.affiliation: *Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Duarte
authors.affiliation: *Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lima
authors.affiliation: *Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Maria
authors.affiliation: *Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Prando
authors.affiliation: *Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Deisy Y
authors.initials: DY
authors.lastname: Rodríguez
authors.affiliation: *Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Geisa A
authors.initials: GA
authors.lastname: Santos
authors.affiliation: ‡Department of Physiology and Pathology, Faculty of Dentistry at Araraquara, Univ. Estudual Paulista, 14801-903, Araraquara, SP, Brazil.
authors.forename: Pedro P C
authors.initials: PP
authors.lastname: Souza
authors.affiliation: *Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Lucas T
authors.initials: LT
authors.lastname: Parreiras-E-Silva
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D001862:Bone Resorption; D001920:Bradykinin / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007705:Kinins / Q000378:metabolism*; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000071557:beta-Arrestins
chemical_list: D000809:Angiotensins; D019390:Arrestins; D007705:Kinins; D008024:Ligands; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D000804:Angiotensin II; D001920:Bradykinin