title: The role of endocytosis in renal dopamine D1 receptor signaling.
abstract: Desensitization of G-protein-coupled receptors (GPCR) includes receptor endocytosis. This phenomenon is suggested, at least for some receptors, to be associated with receptor resensitization. Here, we examined the role of receptor endocytosis for two different GPCR, the dopamine-1 (D1) receptor and the beta1-adrenoceptor (beta(1)-AR) in renal tissue. The functional role of receptor endocytosis was examined on Na+, K+ -ATPase activity in microdissected proximal tubules from rat kidney. The spatial regulation of endogenous D1 receptors and beta(1)-AR was examined by confocal microscopy techniques in LLCPK cells. Phenylarsine oxide (PAO) an endocytosis inhibitor, attenuated isoproterenol-induced decrease in Na+, K+ -ATPase activity but had no such effect on dopamine-induced decrease in Na+, K+ -ATPase activity. We have previously shown that isoproterenol sensitizes the renal dopamine system, by recruiting silent D1 receptors from the interior of the cell towards the plasma membrane. This effect was attenuated by PAO as well as by cytochalasin D while these substances had no effect on dopamine-induced D1 receptor recruitment. The beta(1)-AR was localized to the plasma membrane in control cells. Isoproterenol induced a rapid internalization of the beta(1)-AR; which was prevented by PAO. The results suggest that endocytosis of beta(1)-AR in renal proximal tubular cells is an important step in signal generation, while endocytosis of proximal tubular D1 receptor is not.
authors.affiliation: Department of Woman and Child Health, Pediatric Unit, Astrid Lindgren Children's Hospital, Karolinska Institute, 17176 Stockholm, Sweden.
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Brismar
authors.forename: Xiang
authors.initials: X
authors.lastname: Hua
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Adachi
authors.forename: Ulla
authors.initials: U
authors.lastname: Holtbäck
mesh_terms: D000818:Animals; D001152:Arsenicals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine
chemical_list: D001152:Arsenicals; D017447:Receptors, Dopamine D1; C029341:oxophenylarsine; D000242:Cyclic AMP; D007545:Isoproterenol; D004298:Dopamine