Role of GABA receptors in fetal lung development in rats

• Published in: PloS one 2010-11, Vol.5 (11), p.e14171
• Main Authors: Chintagari, Narendranath Reddy, Jin, Nili, Gao, Li, Wang, Yang, Xi, Dong, Liu, Lin
• Format: Article
• Language: English
• Subjects: Acids; Actin; Actins - metabolism; Alveoli; Animals; Bicuculline; Bicuculline - pharmacology; Biology; Body weight; Body Weight - drug effects; Butyric acid; Cell proliferation; Cell Proliferation - drug effects; Chloride ions; Chlorides - metabolism; Cystic fibrosis; Developmental Biology; Distension; Efflux; Endoscopy; Enzymes; Epithelial cells; Epithelium; Female; Fetuses; Fluxes; GABA; GABA Agents - pharmacology; GABA-A Receptor Antagonists - pharmacology; gamma-Aminobutyric Acid - metabolism; gamma-Aminobutyric Acid - pharmacology; Gastroesophageal reflux; Gestation; Glutamate; Glutamate decarboxylase; Glutamate Decarboxylase - metabolism; Glutamic acid; Hernias; Immunohistochemistry; Ion Transport - drug effects; Laboratories; Lung - cytology; Lung - embryology; Lung - metabolism; Lungs; Male; Modulators; Molecular Biology; Mortality; Muscle, Smooth - chemistry; Myofibroblasts - drug effects; Myofibroblasts - metabolism; Organ Size - drug effects; Organogenesis - physiology; Phosphates; Physiological aspects; Physiology; Physiology/Respiratory Physiology; Pregnancy; Protein C; Rats; Rats, Sprague-Dawley; Receptors; Receptors, GABA-A - metabolism; Receptors, GABA-A - physiology; Rodents; Saccule; Secretion; Smooth muscle; Stem cells; Surfactant protein C; Surgery; Time Factors; Toxicology; γ-Aminobutyric acid A receptors; γ-Aminobutyric acid receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014171

Fluid accumulation is critical for lung distension and normal development. The multi-subunit γ-amino butyric acid type A receptors (GABAA) mainly act by mediating chloride ion (Cl-) fluxes. Since fetal lung actively secretes Cl--rich fluid, we investigated the role of GABAA receptors in fetal lung development. The physiological ligand, GABA, and its synthesizing enzyme, glutamic acid decarboxylase, were predominantly localized to saccular epithelium. To examine the effect of activating GABAA receptors in fetal lung development in vivo, timed-pregnant rats of day 18 gestation underwent an in utero surgery for the administration of GABAA receptor modulators into the fetuses. The fetal lungs were isolated on day 21 of gestation and analyzed for changes in fetal lung development. Fetuses injected with GABA had a significantly higher body weight and lung weight when compared to phosphate-buffered saline (control)-injected fetuses. GABA-injected fetal lungs had a higher number of saccules than the control. GABA increased the number of alveolar epithelial type II cells as indicated by surfactant protein C-positive cells. However, GABA decreased the number of α-smooth muscle actin-positive myofibroblasts, but did not affect the number of Clara cells or alveolar type I cells. GABA-mediated effects were blocked by the GABAA receptor antagonist, bicuculline. GABA also increased cell proliferation and Cl- efflux in fetal distal lung epithelial cells. In conclusion, our results indicate that GABAA receptors accelerate fetal lung development, likely through an enhanced cell proliferation and/or fluid secretion.