Urodilatin increases renal dopamine uptake: intracellular network involved

Abstract

Dopamine and urodilatin promote natriuresis and diuresis through a common pathway that involves reversible deactivation of renal Na+, K+-ATPase. We have reported that urodilatin enhances dopamine uptake in outer renal cortex through the natriuretic peptide type A receptor. Moreover, urodilatin enhances dopamine-induced inhibition of Na+, K+-ATPase activity. The objective of the present work was to investigate the intracellular signals involved in urodilatin effects on dopamine uptake in renal cortex of kidney rats. We show that urodilatin-elicited increase in ³H-dopamine was blunted by methylene blue (10 μM), a non-specific guanylate cyclase inhibitor, and by phorbol-12-myristate-13-acetate (1 μM), a particulate guanylate cyclase inhibitor, but not by 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (10 μM), a specific soluble guanylate cyclase inhibitor; therefore the involvement of particulate guanylate cyclase on urodilatin mediated dopamine uptake was confirmed. Cyclic guanosine monophosphate and proteinkinase G were also implicated in the signaling pathway, since urodilatin effects were mimicked by the analog 125 μM 8-Br-cGMP and blocked by the proteinkinase G-specific inhibitor, KT-5823 (1 μM). In conclusion, urodilatin increases dopamine uptake in renal cortex stimulating natriuretic peptide type A receptor, which signals through particulate guanylate cyclase activation, cyclic guanosine monophosphate generation, and proteinkinase G activation. Dopamine and urodilatin may achieve their effects through a common pathway that involves deactivation of renal Na+, K+-ATPase, reinforcing their natriuretic and diuretic properties.

Na+‐K+‐ATPase, a potent neuroprotective modulator against Alzheimer disease

“…Furthermore, in kidney, the activation/deactivation of renal Na + , K + ‐ATPase is also a final common pathway for regulation of natriuresis . For example, dopamine and urodilatin achieve their effects through a common pathway that involves deactivation of renal Na + , K + ‐ATPase, reinforcing their natriuretic and diuretic properties . The deficiency in the Na + , K + ‐ATPase activity might be a common pathogenesis of central nervous system disorders, such as central nervous system glioma, multiple sclerosis, systemic lupus erythematosis, subacute sclerosing panencephalitis, primary generalized epilepsy, PD, Down syndrome, syndrome X with multiple lacunar state, several other neurodegenerative disorders, and metabolic diseases .…”

Regulation of Dopamine Uptake by Vasoactive Peptides in the Kidney

“…In this way, we have previously reported that ANP and URO stimulate dopamine uptake by the tubular cells in the kidney through NPR-A receptors coupled to guanylate cyclase and cGMP as second messenger [20, 21]. As a physiological antagonist, Ang II exhibits the opposite effect through AT1R and PKA and cAMP as second messenger [23].…”

“…On the other hand, administration of L-NAME reduced the natriuresis and diuresis elicited by dopamine and decreased urinary nitrate excretion, indicating NO involvement in regulation of renal sodium excretion, and, besides, NO system is required for the full expression of diuretic and natriuretic responses elicited by D1 receptor activation [62]. We have also reported that while inhibition of particulate cGMP inhibits ANP and URO stimulating effects on dopamine uptake in renal tissue, inhibition of soluble cGMP by ODQ lacked effects, suggesting that ANP and URO effects are nondependent on NO [20, 21]. Brouwers et al have reported that AT2 receptors may have a pathophysiological role in modulating renal hemodynamic effects of Ang II in SHR rats [60].…”

“…We have previously demonstrated that ANP and URO, through stimulation of dopamine uptake, favor dopamine intracellular accumulation which in turn results in an overinhibition of Na + , K + -ATPase activity [18, 19]. This process is mediated by the NPR-A-cGMP-PKG intracellular pathway [20, 21]. As a physiological antagonist, Ang II exhibits the opposite effect through AT1R and PKA and cAMP as second messenger [22, 23].…”

Cardiac Natriuretic Peptide System: A Link between Adipose Tissue, Obesity, and Insulin Resistance

“…Another member of the NP system is urodilatin (URO), which is produced by the distal kidney tubules and is considered as a local part of the natriuretic peptide system due to its diuretic effects. It was first found as a 32-amino-acid peptide in urine [29][30][31]. Altogether, each endogenous natriuretic peptide is an inseparable component of the cardiovascular system [32].…”