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(2) 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(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 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.
Barnard
M L
ML
Michael Reese Hospital and Medical Center, Pulmonary and Critical Care Medicine and Northwestern University Medical School, Chicago, Illinois, USA.
Ridge
K M
KM
Saldias
F
F
Friedman
E
E
Gare
M
M
Guerrero
C
C
Lecuona
E
E
Bertorello
A M
AM
Katz
A I
AI
Sznajder
J I
JI
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001693:Biological Transport, Active; D015153:Blotting, Western; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011433:Propranolol / Q000494:pharmacology; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D015222:Sodium Channels; D011433:Propranolol; D004298:Dopamine