Stimulation of the dopamine 1 receptor increases lung edema clearance

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 specific D-1 receptor antagonist) or propranolol (a beta-adrenergic antagonist) did not alter DA-stimulated clearance. Similarly, the specific dopaminergic D-1 agonist fenoldopam increased lung edema clearance, but quinpirole (a specific dopaminergic D-1 agonist) did not. I-125-SCH 23982 binding studies suggested that D-1 receptors are expressed on alveolar type II (ATII) cells with an apparent dissociation constant (K-d) Of 4.4 nM and binding maximum (Bmax) 9.8 pmol/mg. Consistent with these results, 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 mediates DA-stimulated edema removal from rat lungs.