Effects of hyperprolactinemia in a murine model of acute pulmonary inflammation

• Grant number: 15/02441-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2015
• Effective date (End): May 31, 2016
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal Investigator: Adriano Zager
• Grantee: Talita Rossetto Barreto
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Increasing findings indicate an interaction between the immune and nervous systems. For example, the central dopaminergic system can modulate the prolactin neural receptors and their release. In turn, the prolactin is a hormone involved in many biological functions, such as immunomodulation. The physiological control of prolactin secretion is mainly inhibitory, and is done through the activation of dopamine D2 receptors in the pituitary gland. In contrast, blockade of these receptors increases serum prolactin levels. Domperidone is an antagonist drug of dopamine receptors whose mechanism of action is given by the blockade of D2 receptors in the chemoreceptor trigger zone, located outside the blood-brain barrier. In order to study the effects of prolactin in inflammatory processes, we elected to use the model of acute lung injury (ALI), a severe form of lung disease of acute onset, characterized by inflammation and injury to the alveolar-capillary with accumulation of neutrophils and release of pro-inflammatory cytokines. Although the activation of neutrophils is vital to the defense of the host, its overactivation leads to tissue damage by releasing cytotoxic agents and immune system cell recruitment. Therefore, the present study aims to investigate the effects of hyperprolactinemia induced by domperidone in a murine model of ALI, induced by intranasal administration of lipopolysaccharide (LPS), within a neuroimmune perspective.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BARRETO, TALITA ROSSETTO; COSTOLA-DE-SOUZA, CAROLINA; MARGATHO, RAFAEL OLIVEIRA; QUEIROZ-HAZARBASSANOV, NICOLLE; RODRIGUES, SANDRA CAMPOS; FELICIO, LUCIANO FREITAS; PALERMO-NETO, JOAO; ZAGER, ADRIANO. Repeated Domperidone treatment modulates pulmonary cytokines in LPS-induced acute lung injury in mice. International Immunopharmacology, v. 56, p. 43-50, MAR 2018. (15/02441-0, 16/22364-2, 13/18921-5, 09/51886-3)