Sorting nexin 1 loss results in D5 dopamine receptor dysfunction in human renal proximal tubule cells and hypertension in mice

摘要: The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. dopamine D5 receptor (D5R) interacts with sorting nexin 1 (SNX1), protein involved retrieval from the trans-Golgi network. In this report, we elucidated spatial, temporal, functional significance of interaction human proximal tubule cells HEK293 stably expressing D5R mice. Silencing SNX1 expression via RNAi resulted failure to internalize bind GTP, blunting agonist-induced increase cAMP production decrease sodium transport, up-regulation angiotensin II expression, which was previously shown be negatively regulated by D5R. Moreover, siRNA-mediated depletion C57BL/6J BALB/cJ mice increased blunted natriuretic response agonist salt-loaded These data demonstrate for trafficking that results dysfunction thus may represent novel mechanism pathogenesis essential hypertension.