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Published on: July 7, 2017
Short-Term Hyperprolactinemia Reduces the Expression of Purinergic P2X7 Receptors during Allergic Inflammatory
Julieta E Ochoa-Amaya1,2, Nicolle Queiroz-Hazarbassanov1, Lilian B Namazu1
1Departamento de Patologia da Faculdade de Medicina Veterinária da Universidade de São Paulo, São Paulo, Brazil.
Purpose:
We have previously shown that domperidone-induced short-term hyperprolactinemia reduces the lung's allergic inflammatory response in an ovalbumin antigenic challenge model. Since purinergic receptor P2X7R activity leads to proinflammatory cytokine release and is possibly related to the pathogenesis of allergic respiratory conditions, the present study was designed to investigate a possible involvement of purinergic and prolactin receptors in this phenomenon.
Methods:
To induce hyperprolactinemia, domperidone was injected intraperitoneally in rats at a dose of 5.1 mg × kg-1 per day for 5 days. P2X7 expression was evaluated by lung immunohistochemistry while prolactin receptor expression in bronchoalveolar lavage leukocytes was analyzed through flow cytometry.
Results:
Previous reports demonstrated that rats subjected to short-term hyperprolactinemia exhibited a decrease in leukocyte counts in bronchoalveolar lavage, especially granulocytes. Here, it is revealed that hyperprolactinemia promotes an increased expression of prolactin receptors in granulocytes. Also, increased expression of purinergic P2X7R observed in allergic animals was significantly reduced by hyperprolactinemia.
Conclusions:
Both purinergic and prolactin receptor expression changes occur during the anti-asthmatic effect of hyperprolactinemia.
Insights
Short-term hyperprolactinemia, induced by domperidone, reduces allergic lung inflammation by altering prolactin and P2X7 receptors. This suggests a novel therapeutic pathway for allergic respiratory conditions.
Area of Science:
- Immunology
- Respiratory Medicine
- Endocrinology
Background:
- Domperidone-induced hyperprolactinemia has been shown to reduce allergic lung inflammation.
- Purinergic receptor P2X7R activity is linked to proinflammatory cytokine release and allergic respiratory disease pathogenesis.
Purpose of the Study:
- To investigate the involvement of purinergic and prolactin receptors in the anti-allergic effects of hyperprolactinemia.
- To explore the role of P2X7R and prolactin receptors in domperidone-induced hyperprolactinemia's impact on allergic lung inflammation.
Main Methods:
- Hyperprolactinemia was induced in rats via daily intraperitoneal injections of domperidone.
- Lung P2X7 receptor expression was assessed using immunohistochemistry.
- Prolactin receptor expression in bronchoalveolar lavage leukocytes was analyzed by flow cytometry.
Main Results:
- Hyperprolactinemia increased prolactin receptor expression in granulocytes.
- Allergic conditions showed increased P2X7 receptor expression, which was significantly reduced by hyperprolactinemia.
- Leukocyte counts, particularly granulocytes, in bronchoalveolar lavage decreased under hyperprolactinemia.
Conclusions:
- Changes in both purinergic and prolactin receptor expression are associated with the anti-asthmatic effect of hyperprolactinemia.
- These receptor alterations may mediate the reduction in allergic lung inflammation observed in hyperprolactinemic states.
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