Role of GABA Receptors in Fetal Lung Development in Rats

Chintagari, Narendranath Reddy; Jin, Nili; Gao, Li; Wang, Yang; Dong, Xi; Lin, Li-Yun

doi:10.1371/journal.pone.0014171

Cited by 13 publications

(17 citation statements)

References 48 publications

(64 reference statements)

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“…Immunohistochemistry was performed as previously reported [11] . The formalin-fixed tissues were de-paraffinized and subjected to antigen retrieval.…”

Section: Methodsmentioning

confidence: 99%

Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease

Chintagari

Nguyen

Belcher

et al. 2015

Blood Cells, Molecules, and Diseases

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Sickle cell disease (SCD), a hereditary hemolytic disorder is characterized by chronic hemolysis, oxidative stress, vaso-occlusion and end-organ damage. Hemolysis releases toxic cell-free hemoglobin (Hb) into circulation. Under physiologic conditions, plasma Hb binds to haptoglobin (Hp) and forms Hb-Hp dimers. The dimers bind to CD163 receptors on macrophages for further internalization and degradation. However, in SCD patients plasma Hp is depleted and free Hb is cleared primarily by proximal tubules of kidneys. Excess free Hb in plasma predisposes patients to renal damage. We hypothesized that administration of exogenous Hp reduces Hb-mediated renal damage. To test this hypothesis, human renal proximal tubular cells (HK-2) were exposed to HbA (50 μM heme) for 24 hours. HbA increased the expression of heme oxygenase-1 (HO-1), an enzyme which degrades heme, reduces heme-mediated oxidative toxicity, and confers cytoprotection. Similarly, infusion of HbA (32 μM heme/kg) induced HO-1 expression in kidneys of SCD mice. Immunohistochemistry confirmed the increased HO-1 expression in the proximal tubules of the kidney. Exogenous Hp attenuated the HbA-induced HO-1 expression in vitro and in SCD mice. Our results suggest that Hb-mediated oxidative toxicity may contribute to renal damage in SCD and that Hp treatment reduces heme/iron toxicity in the kidneys following hemolysis.

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“…Immunohistochemistry was performed as previously reported [11] . The formalin-fixed tissues were de-paraffinized and subjected to antigen retrieval.…”

Section: Methodsmentioning

confidence: 99%

Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease

Chintagari

Nguyen

Belcher

et al. 2015

Blood Cells, Molecules, and Diseases

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“…Beyond that, GABA-receptors are found in the lungs 56,57 . There, activation of GABA A -receptors leads to airway smooth muscle relaxation 58–62 and plays a role in the fetal development of the lung 63,64 .…”

Section: Discussionmentioning

confidence: 99%

Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation

Suleiman

Klassen

Katz

et al. 2019

Sci Rep

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Argon exerts neuroprotection. Thus, it might improve patients’ neurological outcome after cerebral disorders or cardiopulmonary resuscitation. However, limited data are available concerning its effect on pulmonary vessel and airways. We used rat isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of rats and humans to assess this topic. IPL: Airway and perfusion parameters, oedema formation and the pulmonary capillary pressure (Pcap) were measured and the precapillary and postcapillary resistance (Rpost) was calculated. In IPLs and PCLS, the pulmonary vessel tone was enhanced with ET-1 or remained unchanged. IPLs were ventilated and PCLS were gassed with argon-mixture or room-air. IPL: Argon reduced the ET-1-induced increase of Pcap, Rpost and oedema formation (p < 0.05). PCLS (rat): Argon relaxed naïve pulmonary arteries (PAs) (p < 0.05). PCLS (rat/human): Argon attenuated the ET-1-induced contraction in PAs (p < 0.05). Inhibition of GABAB-receptors abolished argon-induced relaxation (p < 0.05) in naïve or ET-1-pre-contracted PAs; whereas inhibition of GABAA-receptors only affected ET-1-pre-contracted PAs (p < 0.01). GABAA/B-receptor agonists attenuated ET-1-induced contraction in PAs and baclofen (GABAB-agonist) even in pulmonary veins (p < 0.001). PLCS (rat): Argon did not affect the airways. Finally, argon decreases the pulmonary vessel tone by activation of GABA-receptors. Hence, argon might be applicable in patients with pulmonary hypertension and right ventricular failure.

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“…It is possible that GABA mediates Cl - influxes in the lung under injurious conditions. GABA receptors have been shown to switch the Cl - conductance patterns in fetal and adult cells, depending on intracellular Cl - concentrations [14,16,58]. …”

Section: Discussionmentioning

confidence: 99%

“…CFTR-mediated Cl - influx results in fluid resorption [9,10]. Water is resorbed by aquaporins expressed on AEC I. Conversely, Cl - effluxes have also been reported [11-14]. Thus, AEC II can mediate the movement of Cl - in both directions.…”

Section: Introductionmentioning

confidence: 99%

GABA receptor ameliorates ventilator-induced lung injury in rats by improving alveolar fluid clearance

Chintagari

Lin

2012

Critical Care

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IntroductionMechanical ventilators are increasingly used in critical care units. However, they can cause lung injury, including pulmonary edema. Our previous studies indicated that γ-aminobutyric acid (GABA) receptors are involved in alveolar-fluid homeostasis. The present study investigated the role of GABA receptors in ventilator-induced lung injury.MethodsAdult female Sprague-Dawley rats were subjected to high-tidal-volume ventilation of 40 ml/kg body weight for 1 hour, and lung injuries were assessed.ResultsHigh-tidal-volume ventilation resulted in lung injury, as indicated by an increase in total protein in bronchoalveolar fluid, wet-to-dry ratio (indication of pulmonary edema), and Evans Blue dye extravasation (indication of vascular damage). Intratracheal administration of GABA before ventilation significantly reduced the wet-to-dry ratio. Further, histopathologic analysis indicated that GABA reduced ventilator-induced lung injury and apoptosis. GABA-mediated reduction was effectively blocked by the GABAA-receptor antagonist, bicuculline. The GABA-mediated effect was not due to the vascular damage, because no differences in Evans Blue dye extravasation were noted. However, the decrease in alveolar fluid clearance by high-tidal-volume ventilation was partly prevented by GABA, which was blocked by bicuculline.ConclusionsThese results suggest that GABA reduces pulmonary edema induced by high-tidal-volume ventilation via its effects on alveolar fluid clearance and apoptosis.

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Role of GABA Receptors in Fetal Lung Development in Rats

Cited by 13 publications

References 48 publications

Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease

Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease

Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation

GABA receptor ameliorates ventilator-induced lung injury in rats by improving alveolar fluid clearance

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