Prolactin and dopamine 1-like receptor interaction in renal proximal tubular cells

Abstract

Prolactin is a natriuretic hormone and acts by inhibiting the activity of renal tubular Na(+)-K(+)-ATPase activity. These effects require an intact renal dopamine system. Here, we have studied by which mechanism prolactin and dopamine interact in Sprague-Dawley rat renal tissue. Na(+)-K(+)-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected renal proximal tubular segments. Intracellular signaling pathways were studied by a variety of different techniques, including Western blotting using phosphospecific antibodies, immunoprecipitation, and biotinylation assays. We found that dopamine and prolactin regulated Na(+)-K(+)-ATPase activity via similar signaling pathways, including protein kinase A, protein kinase C, and phosphoinositide 3-kinase activation. The cross talk between prolactin and dopamine 1-like receptors was explained by a heterologous recruitment of dopamine 1-like receptors to the plasma membrane in renal proximal tubular cells. Prolactin had no effect on Na(+)-K(+)-ATPase activity in spontaneously hypertensive rats, a rat strain with a blunted response to dopamine. These results further emphasize the central role of the renal dopamine system in the interactive regulation of renal tubular salt balance.

Gastrin and D 1 Dopamine Receptor Interact to Induce Natriuresis and Diuresis

“…While several GPCRs and other hormones/humoral factors have been reported to positively interact with the D 1 R in the regulation of sodium excretion, including atrial natriuretic peptide (ANP)/ANPA 47 , AT 2 R 48 , nitric oxide 49 , and prolactin 50 , the role of such interactions in hypertension has not been reported. Our present study finds that CCK B R is another GPCR that positively interacts with the D 1 R in the regulation sodium excretion.…”

Potential Dopamine-1 Receptor Stimulation in Hypertension Management

“…Other natriuretic factors (ANP/ANPA, eicosanoids, nitric oxide, urodilatin) also regulate D1-like receptor function [67][68][69][70]. It is likely that D1-like receptor may play a central role in the natriuretic effects of these factors, as has been shown for prolactin [53]. The cellular levels of insulin and glucose may also regulate D1 receptor function.…”

“…Other natriuretic and anti-natriuretic factors interact with and regulate D1 receptor function. Prolactin produces natriuresis in part by interacting with D-like receptor and inhibiting renal proximal tubular Na/KATPase activity [53]. Renal D1-like receptor seems to play a central role in this phenomenon, as prolactin-mediated inhibition of Na/K-ATPase is attenuated in SHRs harboring desensitized renal D1 receptor [53].…”

“…Prolactin produces natriuresis in part by interacting with D-like receptor and inhibiting renal proximal tubular Na/KATPase activity [53]. Renal D1-like receptor seems to play a central role in this phenomenon, as prolactin-mediated inhibition of Na/K-ATPase is attenuated in SHRs harboring desensitized renal D1 receptor [53]. Renal angiotensin II (AT), an antinatriuretic hormone, exerts its effects primarily through the stimulation of AT type 1 (AT1) receptor, leading to sodium reabsorption by the proximal tubule of the kidney.…”

Genetics of Salt-Sensitive Hypertension

“…In mammals, the effects of dopamine are exerted via two families of receptors belonging to the superfamily of G protein–coupled receptors: D 1 -like receptors, comprised of D 1 R and D 5 R; and D 2 -like receptors, comprised of D 2 R, D 3 R, and D 4 R. During conditions of mild volume and sodium excess, dopamine in the kidney is responsible for more than 50% to 60% of sodium excretion [31, 86, 87], either by itself or via a synergistic interaction with other natriuretic factors such as ANP/ANPA [88], eicosanoids [89, 90], endothelin/ETBR [91], insulin [92], nitric oxide [93], prolactin [94], urodilatin [88], angiotensin III/AT 2 R [41], and inhibition of renin, AT 1 R [87, 95, 96], and aldosterone [89]. The inhibition of renal transport of sodium and other ions occurs in multiple segments of the nephron, including proximal and distal convoluted tubule, thick ascending limb of Henle, and cortical collecting ducts [31, 74, 75, 86, 87, 95, 96, 97•, 98, 99].…”