Endogenous renal dopamine production regulates phosphate excretion

Abstract

We examined the effect of endogenous dopamine production on Pi and citrate excretion by Wistar rats. Carbidopa (20-40 mumol/kg ip) decreased dopamine, Pi, and citrate excretion within 20 min (86%, 47%, and 38%, respectively); Pi reabsorption increased 11 +/- 4% (P = 0.03). The decreases were sustained for at least 18 h. 3-Hydroxybenzylhydrazine (45 mumol/kg ip) reduced Pi excretion 24%. Benserazide (40 mumol/kg ip and 0.1 mumol/min iv) reduced dopamine excretion (94%) and blocked the effect of carbidopa on Pi and citrate excretion. In isolated perfused kidneys benserazide, carbidopa, and 3-hydroxybenzylhydrazine all decreased Pi excretion. Dopamine (1 mumol/l) added to cortical minceates reduced brush-border membrane vesicle (BBMV) 32P uptake by 8% (P < 0.02) and amiloride-inhibitable 22Na uptake by 19%. Carbidopa added to minceates increased 32P uptake by 12%. Carbidopa pretreatment increased (75%) amiloride-sensitive 22Na uptake into BBMV of rats fed a high-salt diet. Uptake was not increased into BBMV from rats fed a low-salt diet. Carbidopa increased (17%) basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) gradually over 4 h. Na(+)-K(+)-ATPase did not increase in rats fed a low-phosphorous diet, but did increase when dopa was added to the diet. Thus endogenous dopamine appears to directly control Na(+)-Pi and Na+/H+ transport and secondarily alter basolateral membrane Na(+)-K(+)-ATPase.

Signaling pathways utilized by PTH and dopamine to inhibit phosphate transport in mouse renal proximal tubule cells

“…In other studies, cells were incubated in 8-bromo-cAMP (100 M) or 8-pCPT-2Ј-O-Me-cAMP (50 M) for 25 min before study. Phosphate transport was measured by determination of the sodium-dependent uptake of 32 P-labeled phosphate (9,11). The cells were washed three times and preincubated for 5 min in nonradioactive transport medium containing 137 mM NaCl, 5.0 mM KCl, 1.0 mM CaCl 2, 1.8 mM MgSO 4, and 0.1 mM KH2PO4.…”

G protein-coupled receptor kinase 4 gene variants in human essential hypertension

“…In addition, disruption of the D 1 receptor in mice produces hypertension (12, 13). The pivotal role of dopamine in the excretion of sodium after increased sodium intake has led to the hypothesis that an aberrant renal dopaminergic system is important in the pathogenesis of some forms of genetic hypertension (3,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Several mechanisms potentially responsible for the failure of endogenous renal dopamine to engender a natriuretic effect in genetic hypertension have been investigated and ruled out, including decreased renal dopamine production and receptor expression, aberrant nephron segment distribution of dopamine receptors, defective effector enzymes (adenylyl cyclase or phospholipase C), and abnormal renal sodium transporters (3,8,13,17).…”

“…Several mechanisms potentially responsible for the failure of endogenous renal dopamine to engender a natriuretic effect in genetic hypertension have been investigated and ruled out, including decreased renal dopamine production and receptor expression, aberrant nephron segment distribution of dopamine receptors, defective effector enzymes (adenylyl cyclase or phospholipase C), and abnormal renal sodium transporters (3,8,13,17). Also, the coding region of the D 1 receptor is unchanged in hypertensive subjects (16), as well as in rodents with genetic hypertension (unpublished studies).In renal proximal tubules from humans with essential hypertension and from rodents with genetic hypertension, the D 1 -like receptor is uncoupled from its G protein͞effector enzyme complex (3,(7)(8)(9)(10)16). This uncoupling is thought to be the mechanism for the failure of dopamine to engender a natriuresis in genetic hypertension (3,5,(11)(12)(13)(14)(15).…”

“…In renal proximal tubules from humans with essential hypertension and from rodents with genetic hypertension, the D 1 -like receptor is uncoupled from its G protein͞effector enzyme complex (3,(7)(8)(9)(10)16). This uncoupling is thought to be the mechanism for the failure of dopamine to engender a natriuresis in genetic hypertension (3,5,(11)(12)(13)(14)(15).…”

“…The paracrine͞ autocrine dopaminergic regulation of sodium excretion is mediated by tubular but not by hemodynamic mechanisms (6). The ability of dopamine and D 1 -like agonists to decrease renal proximal tubular sodium reabsorption is impaired in genetic rodent hypertension and human essential hypertension (3,5,(7)(8)(9)(10)(11)(12)(13)(14)(15). Indeed, the aberrant D 1 -like receptor function in the kidney precedes and cosegregates with high blood pressure in spontaneously hypertensive rats.…”