Crosstalk between dopamine receptors and the Na+/K+-ATPase (Review)

Abstract

Abstract. Dopamine (DA) receptors, which belong to the G protein-coupled receptor family, are the target of ~50% of all modern medicinal drugs and constitute a large and diverse class of proteins whose primary function is to transduce extracellular stimuli into intracellular signals. Na + /K + -ATPase (NKA) is ubiquitous and crucial for the maintenance of intracellular ion homeostasis and excitability. Furthermore, it plays a critical role in diverse effects, including clinical cardiotonic and cardioprotective effects, ischemic preconditioning in the brain, natriuresis, lung edema clearance and other processes. NKA regulation is of physiological and pharmacological importance and has species-and tissue-specific variations. The activation of DA receptors regulates NKA expression/activity and trafficking in various tissues and cells, for example in the kidney, lung, intestine, brain, non-pigmented ciliary epithelium and the vascular bed. DA receptor-mediated regulation of NKA mediates a diverse range of cellular responses and includes endocytosis/exocytosis, phosphorylation/dephosphorylation of the α subunit of NKA and multiple signaling pathways, including phosphatidylinositol (PI)-phospholipase C/protein kinase (PK) C, cAMP/PKA, PI3K, adaptor protein 2, tyrosine phosphatase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase. Furthermore, in brain and HEK293T cells, D 1 and D 2 receptors exist in a complex with NKA. Among D 1 and D 2 receptors and NKA, regulations are reciprocal, which leads to crosstalk between DA receptors and NKA. In the present study, the current understanding of signaling mechanisms responsible for the crosstalk between DA receptors and NKA, as well as with specific consequent functions, is reviewed.

Atrial Natriuretic Peptide and Renal Dopaminergic System: A Positive Friendly Relationship?

“…Dopamine inhibition of Na + , K + -ATPase and other tubular sodium transporters was then confirmed by different experimental studies [6]. Through this mechanism, most of the hormonal factors related to sodium excretion exert their natriuretic actions [2, 14, 31, 43].…”

“…After that, several reports clearly demonstrated that the intrarenal synthetized dopamine constitutes a peripheral dopaminergic system and that renal dopamine is a modulator of blood pressure, sodium balance, and renal functions, independently of the neural dopaminergic system [3]. The importance of dopamine as a natriuretic hormone is reflected through its capacity to inhibit the majority of renal tubule sodium transporters [2, 6]. Notably, the activity of Na + , K + -ATPase is inhibited in most of the tubular segments by dopamine, where it acts by opposing the effects of antinatriuretic factors, such as angiotensin II (ANG II) [6, 7].…”

“…The importance of dopamine as a natriuretic hormone is reflected through its capacity to inhibit the majority of renal tubule sodium transporters [2, 6]. Notably, the activity of Na + , K + -ATPase is inhibited in most of the tubular segments by dopamine, where it acts by opposing the effects of antinatriuretic factors, such as angiotensin II (ANG II) [6, 7]. …”

Hypothesizing that, A Pro-Dopamine Regulator (KB220Z) Should Optimize, but Not Hyper-Activate the Activity of Trace Amine-Associated Receptor 1 (TAAR-1) and Induce Anti-Craving of Psychostimulants in the Long-Term

“…Because of certain genetic precursors and environmental impacts (epigenetics), an insufficiency of D2 receptors may affect individuals as high-risk for several addictive, impulsive, and compulsive behaviors [36]. It is well known that alcohol and other drugs of abuse, as well as most positive reinforcers (i.e., sex, food, gambling, aggressive thrills) cause activation and neuronal release of brain dopamine and involvement of the Na +/ K +− ATPase [37]. Dopamine release can decrease negative feelings and satisfy abnormal cravings for alcohol, cocaine, heroin and nicotine, which including others, are associated with reduced dopamine activity [38].…”

Kidney tubules

“…D 1 -like receptors inhibit salt and water transport in tubular cells, relax vascular smooth muscle, and inhibit sympathetic nervous system activity [34,35]. Stimulation of D 1 -like receptors is associated with natriuresis and diuresis in states of sodium loading, without a requirement for increased renal blood flow [36,37]. During sodium depletion, the effects of D 1 -like receptor ligation are largely lost, with recent work implicating an interaction with the renin–angiotensin signaling pathway [38▪▪].…”