7 research outputs found
Ī² -Adrenergic Stimulation Restores Rat Lung Ability to Clear Edema in Ventilator-associated Lung Injury
Time course of active and passive liquid and solute movement in the isolated perfused rat lung model
Dopamine-induced Exocytosis of Na,K-ATPase Is Dependent on Activation of Protein Kinase C-Īµ and -Ī“
The purpose of this study was to define mechanisms by which dopamine (DA) regulates the Na,K-ATPase in alveolar epithelial type 2 (AT2) cells. The Na,K-ATPase activity increased by twofold in cells incubated with either 1 Ī¼M DA or a dopaminergic D(1) agonist, fenoldopam, but not with the dopaminergic D(2) agonist quinpirole. The increase in activity paralleled an increase in Na,K-ATPase Ī±1 and Ī²1 protein abundance in the basolateral membrane (BLM) of AT2 cells. This increase in protein abundance was mediated by the exocytosis of Na,K-pumps from late endosomal compartments into the BLM. Down-regulation of diacylglycerol-sensitive types of protein kinase C (PKC) by pretreatment with phorbol 12-myristate 13-acetate or inhibition with bisindolylmaleimide prevented the DA-mediated increase in Na,K-ATPase activity and exocytosis of Na,K-pumps to the BLM. Preincubation of AT2 cells with either 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide (Gƶ6983), a selective inhibitor of PKC-Ī“, or isozyme-specific inhibitor peptides for PKC-Ī“ or PKC-Īµ inhibited the DA-mediated increase in Na,K-ATPase. PKC-Ī“ and PKC-Īµ, but not PKC-Ī± or -Ī², translocated from the cytosol to the membrane fraction after exposure to DA. PKC-Ī“ā and PKC-Īµāspecific peptide agonists increased Na,K-ATPase protein abundance in the BLM. Accordingly, dopamine increased Na,K-ATPase activity in alveolar epithelial cells through the exocytosis of Na,K-pumps from late endosomes into the basolateral membrane in a mechanism-dependent activation of the novel protein kinase C isozymes PKC-Ī“ and PKC-Īµ