Stimulation of the dopamine 1 receptor increases lung edema clearance.

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 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.

• Authors: M L Barnard, K M Ridge, F Saldias, E Friedman, M Gare, C Guerrero, E Lecuona, A M Bertorello, A I Katz, J I Sznajder
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 160 Issue 3 Pg. 982-6 (Sep 1999) ISSN: 1073-449X [Print] United States
• PMID: 10471628 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenergic beta-Antagonists
• Dopamine Antagonists
• Receptors, Dopamine
• Sodium Channels
• Propranolol
• Dopamine

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Analysis of Variance
• Animals
• Binding, Competitive
• Biological Transport, Active
• Blotting, Western
• Dopamine (pharmacology)
• Dopamine Antagonists (pharmacology)
• Dose-Response Relationship, Drug
• Propranolol (pharmacology)
• Pulmonary Edema (drug therapy, metabolism)
• Rats
• Receptors, Dopamine (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sodium Channels (metabolism)