HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/5/F1059    most recent 00139.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Pedrosa, R. Articles by Soares-da-Silva, P. Search for Related Content PubMed PubMed Citation Articles by Pedrosa, R. Articles by Soares-da-Silva, P.

G_i3 protein-coupled dopamine D₃ receptor-mediated inhibition of renal NHE3 activity in SHR proximal tubular cells is a PLC-PKC-mediated event

¹Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-319 Porto, Portugal; ³Departments of Pediatrics and Physiology and Biophysics, Georgetown University Medical Center, Washington, District of Columbia 20007; and ²Department of Physiology, Case Western Reserve Medical School, Cleveland, Ohio 44106

Submitted 19 April 2004 ; accepted in final form 17 July 2004

This study evaluated the transduction pathway associated with type 3 Na⁺/H⁺ exchanger (NHE3) activity-induced inhibition during dopamine D₃ receptor activation in immortalized renal proximal tubular epithelial cells from the spontaneously hypertensive rat. The dopamine D₃ receptor agonist 7-OH-DPAT decreased NHE3 activity, which was prevented by the D₂-like receptor antagonist S-sulpiride, pertussis toxin (PTX; overnight treatment), and the PKC inhibitor chelerythrine, but not by cholera toxin (overnight treatment), the MAPK inhibitor PD-098059, or the p38 inhibitor SB-203580. The PKA inhibitor H-89 abolished the inhibitory effects of forskolin on NHE3 activity, but not that of 7-OH-DPAT. The phospholipase C (PLC) inhibitor U-73122 prevented the inhibitory effects of 7-OH-DPAT, whereas PDBu and 7-OH-DPAT increased PLC activity and reduced NHE3 activity; downregulation of PKC abolished the inhibitory effects of both PDBu and 7-OH-DPAT on NHE activity. The inhibition of NHE3 activity by GTPS and the prevention of the effect of 7-OH-DPAT by PTX suggest an involvement of a G_i/o protein coupled to the dopamine D₃ receptor. Indeed, the 7-OH-DPAT-induced decrease in NHE3 activity was abolished in cells treated overnight with the anti-G_i3 antibody, but not in cells treated with antibodies against G_q/11, G_s, G, and G_i1,2 proteins. The calcium ionophore A-23187 and the Ca²⁺-ATPase inhibitor thapsigargin increased intracellular Ca²⁺ but did not affect NHE3 activity. However, the inhibitory effects of PDBu and 7-OH-DPAT on NHE3 activity were completely abolished by A-23287 and thapsigargin. It is concluded that inhibition of NHE3 activity by dopamine D₃ receptors coupled to G_i3 proteins is a PLC-PKC-mediated event, modulated by intracellular Ca²⁺.

Na⁺/H⁺ exchange; protein kinases; hypertension

This article has been cited by other articles:

				R. T. Alexander and S. Grinstein Tethering, recycling and activation of the epithelial sodium-proton exchanger, NHE3 J. Exp. Biol., June 1, 2009; 212(11): 1630 - 1637. [Abstract] [Full Text] [PDF]

				A. A. Banday, Y.-S. Lau, and M. F. Lokhandwala Oxidative Stress Causes Renal Dopamine D1 Receptor Dysfunction and Salt-Sensitive Hypertension in Sprague-Dawley Rats Hypertension, February 1, 2008; 51(2): 367 - 375. [Abstract] [Full Text] [PDF]

				M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]

				M. J. Pinho, V. Pinto, M. P. Serrao, P. A. Jose, and P. Soares-da-Silva Underexpression of the Na+-dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R538 - R547. [Abstract] [Full Text] [PDF]

				K. Hodges, R. Gill, K. Ramaswamy, P. K. Dudeja, and G. Hecht Rapid activation of Na+/H+ exchange by EPEC is PKC mediated Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G959 - G968. [Abstract] [Full Text] [PDF]

				C. Zeng, Z. Wang, H. Li, P. Yu, S. Zheng, L. Wu, L. D. Asico, U. Hopfer, G. M. Eisner, R. A. Felder, et al. D3 Dopamine Receptor Directly Interacts With D1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells Hypertension, March 1, 2006; 47(3): 573 - 579. [Abstract] [Full Text] [PDF]