摘要:

Functioning of the β-adrenergic response system is important for successful transition of the neonate from fetal life to breathing air. We characterized the β-adrenergic receptors on human fetal lung type II cells, the cell type responsible for many pulmonary responses sensitive to β-adrenergic stimulation. Type II cells were isolated from human fetal lung explants, and membrane particulates prepared from these cells were used for radioligand binding studies.125I-iodocyanopindoloI, a specific β-adrenergic antagonist, bound to a single class of saturable, high-affinity binding sites on type II cell membranes with a receptor concentration of 78 ± 9 fmol receptor/mg membrane protein, a kdof 79 ± 18 nM, and 958 ±120 receptors per cell. Binding was stereoselective withl-propranolol binding with higher affinity than the inactived-isomer. The binding site had the characteristics of a β2-adrenergic receptor. The order of potency of β-adrenergic agonists was isoproterenol > epinephrine >> norepinephrine. The β2-selective antagonist ICI 118 551 competed for a single class of high-affinity sites. Agonist binding affinity was reduced in the presence of guanyl nucleotides, consistent with receptors coupled to guanine nucleotide binding proteins. β-Adrenergic agonists also stimulated adenylyl cyclase in these membrane preparations.125I-iodocyanopindolol binding to membranes prepared from human fetal lung fibroblasts indicated fewer receptors (404 ± 68) than were present on type II cells. Work by others has suggested a difference in lung function and lung β-adrenergic receptor concentration between males and females. After culturing midgestation human fetal lung for 5 d we found no significant difference between the β-adrenergic receptor number per type II cell for male (820 ± 165) and female (1107 ± 220) specimens. (Pediatr Res 32: 350–355, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Ventilatory parameters and respiratory drive with and without an added acute resistive load were assessed in 11 healthy preterm infants and 11 infants with bronchopulmonary dysplasia (BPD). Lung mechanics (breathing frequency, tidal volume, minute ventilation, compliance, and resistance) were determined with esophageal manometry and pneumotachography. Respiratory drive was assessed by determining the airway pressure measured 100 ms after the onset of an inspiratory effort against an occlusion. Infants were studied at baseline and with an external inspiratory resistive load of 213.7 cm H2O/L/s. Infants with BPD had similar breathing frequency, tidal volume, and minute ventilation, lower compliance, and greater resistance and airway pressure at 100 ms than healthy preterm infants at rest. With loading, healthy preterm infants demonstrated increased airway pressure at 100 ms, whereas infants with BPD showed no change. Although the healthy preterm infants had decreased minute ventilation and tidal volume with loading, decreases in ventilation were greater in the infants with BPD. These data demonstrate that infants with BPD have responded to a chronic intrinsic load with increased drive. However, this may result in decreased ventilatory reserve and hence, a limited ability to adapt to acute pulmonary loads. (Pediatr Res 32: 356–359, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We recently demonstrated that endothelial cells are more susceptible than renal tubular epithelial cells to oxidant injury and that renal tubular epithelial cells with proximal tubular characteristics including porcine proximal tubular epithelial cells, opossum kidney proximal tubular epithelial cells, and normal human kidney cortical epithelial cells are more susceptible to oxidant injury than the distal nephron-derived Madin Darby canine kidney cell line. To determine the basis of this differential response, we evaluated several antioxidant defenses in the five cell lines. Glutathione levels were not significantly different among the five cell lines, but catalase and glutathione reductase levels were significantly (p< 0.01) lower in endothelial cells compared to all renal tubular epithelial cells. Among renal tubular epithelial cells, Madin Darby canine kidney cells had significantly (p< 0.05) higher glutathione peroxidase activity. To further evaluate the role of antioxidant defenses in limiting oxidant injury, we determined two responses to oxidant injury (ATP depletion and51Cr release) when glutathione was depleted with buthionine sulfoxamine and when catalase was inhibited with aminotriazole. Oxidant-induced ATP depletion was accentuated when catalase was inhibited as well as when glutathione was depleted with buthionine sulfoxamine. In contrast, inhibition of catalase had little or no effect on51Cr release, whereas glutathione depletion resulted in accentuated51Cr release. We conclude that the increased susceptibility of endothelial cells to oxidant injury as compared with epithelial cells is associated with lower antioxidant defenses. Disruption of the glutathione redox cycle results in accentuated ATP depletion and lytic injury, whereas inhibition of catalase results in accentuated ATP depletion with little effect on lytic injury. Augmented oxidant-induced ATP depletion without augmented cell lysis suggests that ATP depletion alone may not be a critical mediator of cell death in oxidant stress. (Pediatr Res 32: 360–365, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The influence of oleic, linoleic (LIN), and eicosapentaenoic (EPA) acids incorporated into cellular lipids on susceptibility to O2-induced toxicity was evaluated in Chinese hamster fibroblasts (HA1) using a clonogenic cell survival assay. Fatty acid incorporation was achieved by incubating HA1 cells in 21% O2for 72 h in the presence or absence of media supplemented with 25 μM oleic acid, 25 μM LIN, or 2, 4, and 25 μM EPA. This fatty acid incorporation period increased the percentage of composition in phospholipids 2-fold for oleic acid, 6-fold for LIN, and 6− to 20-fold for EPA. Vitamin E, total glutathione, superoxide dismutase activity, glutathione transferase activity, and catalase activity were unchanged, relative to control, in the 25-μM EPA-treated group, and only total glutathione was elevated in the LIN-treated group. After the incorporation period, the cells were placed in non-fatty acid supplemented media and exposed to 95% O2, and clonogenic survival responses were evaluated at time intervals up to 100 h. Sensitization to O2toxicity in EPA-treated cells was apparent after 24 h of O2exposure, whereas LIN-treated cells were significantly (p< 0.05) sensitized to hyperoxia after 54 h of exposure, indicating that EPA was a more potent sensitizer for O2injury. Furthermore, cells supplemented with 4 and 25 μM EPA were more sensitive to O2toxicity than cells supplemented with 2 μM EPA. In contrast, cells treated with 25 μM oleic acid were significantly more resistant to O2toxicity at 51, 72, and 98 h of O2exposure. The results indicate that incorporation of polyunsaturated fatty acids (LIN or EPA) into the lipids of cultured cells enhances the cytotoxicity associated with exposure to 95% O2, whereas incorporation of a monosaturated fatty acid (oleic acid) reduced the cytotoxicity of 95% O2. These results suggest that O2-induced injury can be modified by alterations in peroxidizable substrates present in cells. (Pediatr Res 32:366–372, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID