Stimulation of the Dopamine 1 Receptor Increases Lung Edema Clearance

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Abstract
We previously reported that lung edema clearance was stimulated by dopamine (DA). The purpose of this study was to determine whether the DA-mediated stimulation of edema clearance occurs via an adrenergic or dopaminergic regulation of alveolar epithelial Na,K-ATPase. When isolated perfused rat lungs were coinstilled with DA and SCH 23390 (a specific D 1 receptor antagonist), there was a dose-dependent attenuation of the stimulatory effects of DA. Coinstillation with S-sulpiride (a spe- cific D 2 receptor antagonist) or propranolol (a b -adrenergic antagonist) did not alter DA-stimulated clearance. Similarly, the specific dopaminergic D 1 agonist fenoldopam increased lung edema clear- ance, but quinpirole (a specific dopaminergic D 2 agonist) did not. 125 I-SCH 23982 binding studies suggested that D 1 receptors are expressed on alveolar type II (ATII) cells with an apparent dissocia- tion constant ( K d ) of 4.4 nM and binding maximum (Bmax) 9.8 pmol/mg. Consistent with these re- sults, the D 1 receptor messenger RNA (mRNA) and protein were detected in ATII cells by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. These data demonstrate a novel mechanism involving the activation of dopaminergic D 1 receptors which medi- ates DA-stimulated edema removal from rat lungs. Barnard ML, Ridge KM, Saldias F, Friedman E, Gare M, Guerrero C, Lecuona E, Bertorello AM, Katz AI, Sznajder JI. Stimulation of the dopamine 1 receptor increases lung edema clearance. AM J RESPIR CRIT CARE MED 1999;160:982-986.