title: Prolactin and dopamine 1-like receptor interaction in renal proximal tubular cells.
abstract: Prolactin is a natriuretic hormone and acts by inhibiting the activity of renal tubular Na(+)-K(+)-ATPase activity. These effects require an intact renal dopamine system. Here, we have studied by which mechanism prolactin and dopamine interact in Sprague-Dawley rat renal tissue. Na(+)-K(+)-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected renal proximal tubular segments. Intracellular signaling pathways were studied by a variety of different techniques, including Western blotting using phosphospecific antibodies, immunoprecipitation, and biotinylation assays. We found that dopamine and prolactin regulated Na(+)-K(+)-ATPase activity via similar signaling pathways, including protein kinase A, protein kinase C, and phosphoinositide 3-kinase activation. The cross talk between prolactin and dopamine 1-like receptors was explained by a heterologous recruitment of dopamine 1-like receptors to the plasma membrane in renal proximal tubular cells. Prolactin had no effect on Na(+)-K(+)-ATPase activity in spontaneously hypertensive rats, a rat strain with a blunted response to dopamine. These results further emphasize the central role of the renal dopamine system in the interactive regulation of renal tubular salt balance.
authors.affiliation: Pediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Crambert
authors.forename: Agneta
authors.initials: A
authors.lastname: Sjöberg
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Eklöf
authors.forename: Fernando
authors.initials: F
authors.lastname: Ibarra
authors.forename: Ulla
authors.initials: U
authors.lastname: Holtbäck
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019921:Biotinylation; D015153:Blotting, Western; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006868:Hydrolysis; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D047468:Immunoprecipitation; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011981:Receptors, Prolactin / Q000378:metabolism*; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D053614:Janus Kinase 2; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011388:Prolactin; D011493:Protein Kinase C; D017447:Receptors, Dopamine D1; D011981:Receptors, Prolactin; D000254:Sodium-Potassium-Exchanging ATPase; C507927:Jak2 protein, rat