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Inactivation of the kinin B2 receptor in areas of dopaminergic action

Grant number: 23/15365-6
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): December 01, 2023
Effective date (End): November 30, 2025
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Frederick Wasinski
Grantee:Juliene de Lima Soares Silva
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:19/07005-4 - Kinin receptor B2 participation in the nervous system with emphasis on the dopaminergic circuit, AP.JP

Abstract

Kinins, including bradykinins and kallidin, are vasoactive peptides activated by binding to specific receptors, known as kinin receptors (B1R and B2R, respectively). These receptors are expressed in healthy tissues and play key roles in regulating vasodilation, blood pressure control, muscle function, inflammatory response and pain perception, thus playing a crucial role in the body. The B2R receptor is widely studied in the central nervous system and is expressed in various regions of the brain, most notably the hippocampus, striatum and cerebral cortex. Our previous studies have shown that animals deficient in the B2R receptor exhibit a reduction in physical activity when subjected to voluntary exercise wheels. In addition, B2R has the ability to interact with the dopamine receptor DrD2, since both are part of the same family of G proteins. Based on this, we believe that B2R can modulate the dopaminergic pathway, influencing the behavioral, motor coordination and cognitive aspects of animals. Dopaminergic neurons, which are widely expressed in the ventral tegmental area (VTA), can be inhibited by the action of gamma-aminobutyric acid (GABA), a neurotransmitter that mainly exerts an inhibitory function in the central nervous system (CNS). Therefore, our aim is to evaluate the consequences of inhibiting B2R signaling in GABAergic neurons (which express the GABA vesicle).

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