Kidney dopamine D₁-like receptors and angiotensin 1–7 interaction inhibits renal Na⁺ transporters

Abstract

The role of dopamine D1-like receptors (DR) in the regulation of renal Na+ transporters, natriuresis, and blood pressure is well established. However, the involvement of the angiotensin 1–7 (ANG 1−7)-Mas receptor in the regulation of Na+ balance and blood pressure is not clear. The present study aimed to investigate the hypothesis that ANG 1–7 can regulate Na+ homeostasis by modulating the renal dopamine system. Sprague-Dawley rats were infused with saline alone (vehicle) or saline with ANG 1–7, ANG 1–7 antagonist A-779, DR agonist SKF38393, and antagonist SCH23390. Infusion of ANG 1–7 caused significant natriuresis and diuresis compared with saline alone. Both natriuresis and diuresis were blocked by A-779 and SCH23390. SKF38393 caused a significant, SCH23390-sensitive natriuresis and diuresis, and A-779 had no effect on the SKF38393 response. Concomitant infusion of ANG 1–7 and SKF38393 did not show a cumulative effect compared with either agonist alone. Treatment of renal proximal tubules with ANG 1–7 or SKF38393 caused a significant decrease in Na+-K+-ATPase and Na+/H+ exchanger isoform 3 activity. While SCH23390 blocked both ANG 1–7- and SKF38393-induced inhibition, the DR response was not sensitive to A-779. Additionally, ANG 1–7 activated PKG, enhanced tyrosine hydroxylase activity via Ser40 phosphorylation, and increased renal dopamine production. These data suggest that ANG 1–7, via PKG, enhances tyrosine hydroxylase activity, which increases renal dopamine production and activation of DR and subsequent natriuresis. This study provides evidence for a unidirectional functional interaction between two G protein-coupled receptors to regulate renal Na+ transporters and induce natriuresis.

An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID‐19

“…3 Along this line, angiotensin 1-7 was shown to stimulate the renal synthesis of dopamine. 4 Conversely, that ACE2 coregulates with DDC also implies that any SARS-CoV2-induced downregulation of ACE2 expression, a process previously demonstrated for SARS-CoV, 5 might be paralleled by alterations of both the dopamine and serotonin synthetic pathways. Supporting this view, ACE2 knockout (KO) mice were reported to exhibit dramatically low serotonin levels in both the blood and brain.…”

Tyrosine hydroxylase conditional KO mice reveal peripheral tissue-dependent differences in dopamine biosynthetic pathways

“…Dopamine (DA) is a neurotransmitter in the brain, and alterations in DA metabolism are related to the pathophysiology of neuropsychiatric disorders, such as Parkinson's disease, schizophrenia, and some developmental disorders. In addition to its role in the brain, DA also plays pivotal physiological functions in peripheral tissues, such as natriuresis in the kidney ( 1 , 2 , 3 ), glucose-stimulated insulin secretion in the pancreas ( 4 , 5 , 6 , 7 ), liquid clearance in the lung ( 8 ), and acid secretion in the stomach ( 9 , 10 ). DA regulates these functions via DA receptors belonging to G protein–coupled receptors.…”

The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension

“…The D 1 R also decreases renal ion transport by interacting with natriuretic hormones and receptors and antinatriuretic hormones and receptors. Thus, the D 1 R adds to the inhibitory effect on ion transport caused by natriuretic hormones, such as angiotensin 1–7 [ 168 ], atrial natriuretic peptide [ 169 ], and prolactin [ 170 ], and receptors such as the angiotensin II type 2 receptor (AT 2 R) [ 171 ], and gastrin/cholecystokinin B receptor (CCKBR) [ 172 ] but decreases the stimulatory effect of renal ion transport caused by angiotensin II (Ang II) [ 166 , 173 ] and α1-adrenergic receptor [ 33 ].…”

“…In general, whereas all five dopamine receptor subtypes inhibit sodium transport [ 120 , 121 ], the AT 1 R increases [ 252 , 253 , 254 ], while the AT 2 R decreases sodium transport [ 171 ]. D 1 -like receptors interact with angiotensin-(1–7) to inhibit renal tubular Na + /K + -ATPase and NHE3 activities [ 168 ]. In this situation, angiotensin-(1–7) increases dopamine production that is not related to receptor/receptor interaction.…”