beta-Adrenoceptor agonist sensitizes the dopamine-1 receptor in renal tubular cells.
The renal effects of dopamine are mainly mediated via the dopamine-1 receptor (D1 receptor). This receptor is recruited from intracellular compartments to the plasma membrane by dopamine and atrial natriuretic peptide (ANP), via adenylyl cyclase activation. We have studied whether isoproterenol, a beta-adrenoceptor (beta-AR) agonist that may interact with dopamine in the regulation of rat renal Na+, K+-adenosine triphosphatase (ATPase) activity, can recruit D1 receptors to the plasma membrane. The spatial regulation of D1 receptors was examined using confocal microscopy techniques in LLCPK cells and the functional interaction between dopamine and isoproterenol was examined by studying their effects on Na+, K+-ATPase activity in microdissected single proximal tubular segments from rat. Isoproterenol was found to translocate the D1 receptors from the interior of the cell towards the plasma membrane. The recruitment of dopamine 1 receptors was found to be cyclic adenosine phosphate (cAMP) dependent, while protein kinase C (PKC) activation was not involved. The functional studies on Na+, K+-ATPase activity showed that the effect of isoproterenol was abolished by a D1-like receptor antagonist (SCH 23390), and mediated via protein kinase A (PKA) and PKC dependent pathways. The results provide an explanation for the interaction between G protein-coupled receptors. The effects of isoproterenol on Na+, K+-ATPase activity can be explained by a heterologous recruitment of D1 receptors to the plasma membrane.
Brismar
H
H
Department Woman and Child Health, Pediatric unit, Karolinska Institutet, Stockholm, Sweden.
Agrèn
M
M
Holtbäck
U
U
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007545:Isoproterenol / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; C027460:dopamine-I receptor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D004298:Dopamine