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GW24-e2366 Stimulation of D3 receptor attenuates renal ischaemia/reperfusion injury via increased its linkage with Gα12
  1. Wang Zhen1,2,
  2. Chunyu Zeng1,2
  1. 1Department of Cardiology, Daping Hospital, The Third Military Medical University
  2. 2Chongqing Institute of Cardiology

Abstract

Objectives Renal ischaemia reperfusion injury (IRI) causes renal tubular necrosis, apoptosis and inflammation leading to acute kidney dysfunction. Recent studies suggest knockout of Gα12 protects from the renal damage during IRI. Inhibition of Gα12 function might be a perspective therapeautic strategy.

Methods Our previous study found the linkage between D3 dopamine receptor (D3R) and Gα12, activation of D3R increased it’s linkage with Gα12, therefore, hampered Gα12-mediated stimulation on sodium reabsorption. Therefore, we hypothesise that silencing Gα12 by increasing protein linkage with D3R, via stimulation of D3 receptor, may contribute to protect against renal IRI. As compared with sham control, IRI worsen renal function and structure, increased renal cellular apoptosis, while pretreatment with D3R agonist PD128907 (0.5 mg/kg, IV) produced significant protection against renal IR injury in Wistar rats. The reactive oxygen species and inflammation might be involved into the D3R-mediated protection, because pretreatment with PD128907 increased renal glutathione (GSH) and SOD levels, decreased MDA level in IRI group. Moreover, the abnormal changes of cytokines, including TNF-α, IL-1β, IL-10 and MPO, were also reversed by activation of D3R.

Results There were co-localisation and co-immunoprecipitation between D3R and Gα12. Activation of D3R increased D3R/Gα12 linkage, hampered the Gα12-induced renal damage.

Conclusions These results suggest that activation of D3R can hampered Gα12-induced renal damage, plays protective effect during IRI.

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