G(i)alpha 3 protein-coupled dopamine D(3) receptor-mediated inhibition of renal NHE3 activity in SHR proximal tubular cells is a PLC-PKC-mediated event

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Pedrosa, R (Author) Other; Pedro Gomes (Author) Other; Hopfer, U (Author) Other; Jose, PA (Author) Other; soares-da-silva, p (Author) FMUP

Journal

Title: American Journal of Physiology - Renal Physiology

Vol. 287

ISSN: 1931-857X

Publisher: American Physiological Society

Indexing

ISI Web of Knowledge - 31 Citations

Scopus - 33 Citations

Other information

Authenticus ID: P-000-7SJ

DOI: 10.1152/ajprenal.00139.2004

Abstract (EN): This study evaluated the transduction pathway associated with type 3 Na(+)/H(+) exchanger (NHE3) activity-induced inhibition during dopamine D(3) receptor activation in immortalized renal proximal tubular epithelial cells from the spontaneously hypertensive rat. The dopamine D(3) receptor agonist 7- OHDPAT decreased NHE3 activity, which was prevented by the D(2)-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- OHDPAT. 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 GTPgammaS 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 D(3) receptor. Indeed, the 7- OH-DPAT-induced decrease in NHE3 activity was abolished in cells treated overnight with the anti-G(i)alpha3 antibody, but not in cells treated with antibodies against G(q/11), G(s)alpha, G(beta), and G(i)alpha1,2 proteins. The calcium ionophore A-23187 and the Ca(2+)-ATPase inhibitor thapsigargin increased intracellular Ca(2+) 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 D(3) receptors coupled to G(i)alpha3 proteins is a PLC-PKC-mediated event, modulated by intracellular Ca(2+).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8