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A Aperia

Publications and source records attributed to A Aperia.

At least 19 recordsLinked to original sources
PubMed1992

Calcineurin mediates alpha-adrenergic stimulation of Na+,K(+)-ATPase activity in renal tubule cells.

The alpha-adrenergic agonist oxymetazoline increased Na+,K(+)-ATPase activity of single proximal convoluted tubules dissected from rat kidney. Activation of the enzyme by oxymetazoline was prevented by either the alpha 1-adrenergic antagonist prazosin or the alpha 2-adrenergic antagonist yohimbine and was mimicked by the calcium ionophore A23187. The effect of oxymetazoline on Na+,K(+)-ATPase activity was prevented by a specific peptide inhibitor of calcineurin, as well as by FK 506, an immunosuppressant agent known to inhibit calcineurin; these results indicate that the action of oxymetazoline is mediated via activation of calcineurin (a calcium/calmodulin-dependent protein phosphatase). Activation of the Na+,K(+)-ATPase by either oxymetazoline or A23187 was associated with a greater than 2-fold increase in its affinity for Na+. The results provide a biochemical mechanism by which norepinephrine, released from renal nerve terminals, stimulates Na+ retention.

Animals↗
PubMed1992

Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats.

The effects of aldose reductase inhibition on kidney function were studied in rats with streptozotocin-induced diabetes mellitus. Diabetic rats were fed sorbinil (20 and 50 mg/kg) by daily gastric gavage and were compared with untreated diabetic rats and normal rats. The rats were under daily supervision with regard to blood glucose control, insulin administration and body weight. The aim was to promote continuous body growth and to maintain the blood glucose concentration at around 22 mmol/l without large day-to-day fluctuations. The renal functional changes observed in this well-established diabetic model closely resembled those reported in human Type 1 (insulin-dependent) diabetes mellitus. Sorbinil treatment completely prevented renal cortical sorbital accumulation, but did not abolish kidney enlargement or the increase in ultrafiltration pressure and glomerular filtration rate. Albumin excretion was increased to the same extent in the sorbinil-treated and in the untreated diabetic rats. We conclude that increased metabolism of glucose to sorbitol does not cause the hyperfiltration in rats with streptozotocin-induced diabetes.

Albuminuria↗
PubMed1992

Renal function in very low birth weight infants: normal maturity reached during early childhood.

Development of glomerular and tubular renal function is delayed in preterm infants. To study the pattern of maturation during infancy and childhood, we re-evaluated renal function in 22 very low birth weight infants--in 14 of the infants at 18 months postconceptional age (9 months corrected age) and in the remaining 8 infants at 8 years of age. The glomerular filtration rate remained lower at 9 months corrected age than in term infants of the same postconceptional age: 82 +/- 23 versus 125 +/- 18 ml/min per 1.73 m2 (p < 0.001). At 8 years of age the glomerular filtration rate did not differ from that of healthy control subjects. Effective renal plasma flow, filtration fraction, albumin excretion, maximal concentrating ability, and kidney size determined by ultrasonography were all normal at 8 years of age. We conclude that renal function, which is markedly reduced during the neonatal period in very low birth weight infants, reaches normal maturity by 8 years of age but not by 9 months corrected age.

Albuminuria↗
PubMed1992

Ontogeny of aromatic L-amino acid decarboxylase-containing tubule cells in rat kidney.

Dopamine plays an important role in regulation of renal sodium transport. Proximal tubule cells produce dopamine after decarboxylation of L-DOPA via the enzyme aromatic L-amino acid decarboxylase (AADC). The presence and cellular localization of AADC-like immunoreactivity (-LI) and AADC mRNA were examined during pre- and postnatal development in rat kidney by indirect immunofluorescence and in situ hybridization histochemistry. Few scattered condensations of AADC-immunoreactive (-IR) tubule cells forming a lumen were detected on gestational day 18. From gestational day 21, many AADC-IR tubule cells were observed in the inner cortex, whereas the outer cortex lacked AADC-LI. Within 24 hours of birth, AADC-IR cells in the inner cortex could be identified as proximal tubule cells. During day 3 and 5 there was an increase in number of AADC-IR proximal tubule cells in the inner cortex, leaving less amount of AADC-negative cells in the outer cortex. Starting from day 8, AADC-IR cells could be seen in the outer cortex. An apparent decrease in AADC-immunofluorescence intensity was observed at 40 days, and at 80 days virtually no AADC-LI could be demonstrated. Intrarenal levels of dopamine showed a tendency to increase between 3 and 20 days, and showed significant decreases between 20 to 40 days and between 40 to 80 days. AADC mRNA was not detected in the kidney at 18 hours after birth, but could be observed in the inner cortex at 6 days. At 12, 19 and 40 days AADC mRNA was seen in the entire cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Control of electrolyte transport in the kidney through a dopamine- and cAMP-regulated phosphoprotein, DARPP-32.

1. DARPP-32 is a phosphoprotein regulated by dopamine and cAMP. In its phosphorylated form it acts as an inhibitor of protein phosphatase-1, thereby regulating the phosphorylation state of phosphoproteins in the basal ganglia. 2. In the kidney, DARPP-32 has been detected in the medullary thick ascending limb of Henle (mTAL) and, to a lesser degree, in the proximal convoluted tubule by means of immunohistochemistry and in situ hybridization. 3. In single microdissected tubules of rat kidney, Na+, K(+)-ATPase activity, measured as ouabain-sensitive ATP hydrolysis, has been shown to be inhibited to the same degree by the DA1 agonist fenoldopam, cAMP and a synthesized and phosphorylated DARPP-32 peptide, D32(8-38). 4. It is concluded that the DA1 receptor-mediated inhibition of Na+ transport in the mTAL by dopamine occurs via cAMP accumulation and the phosphoprotein, DARPP-32.

Animals↗
PubMed1992

Sodium-dependent regulation of sodium, potassium-adenosine-tri-phosphatase (Na+, K(+)-ATPase) activity in medullary thick ascending limb of Henle segments. Effect of cyclic-adenosine-monophosphate guanosine-nucleotide-binding-protein activity and arginine vasopressin.

This study examine the regulation Na+, K(+)-ATPase activity in the medullary thick ascending limb of Henle Na+, K(+)-ATPase activity was determined in medullary thick ascending limb of Henle (mtal) segments dissected from rat kidneys. The sodium concentration in the medium (Nam) was 20 or 70 mM. Since the segments were permeabilized, intracellular Na+ (Nai) was assumed to be the same as Nam. Dibuturyl cyclic adenosine monophosphate (dbcAMP) and forskolin inhibited Na+, K(+)-ATPase activity independently of Nam. Arginine vasopressin (AVP) receptors coupled to adenylate cyclase have been identified in the medullary thick ascending limb of Henle. At Nam = 20 mMAVP caused a dose-dependent inhibition of Na+, K(+)-ATPase activity with a maximal effect (49%) at 10(-8) M. This inhibition was abolished in the presence of the adenylate cyclase inhibitor 2,5-dideoxyadenosine (2, 5-DDA). AVP had no effect on Na+, K(+)-ATPase activity in the mTAL at Nam = 70 mM. The guanosine-diphosphate analogue GDP beta S inhibited Na+, K(+)-ATPase activity at Nam = 70 mM but not at Nam = 20 mM. We conclude that increased cyclic adenosine monophosphate (cAMP) levels inhibit Na+, K(+)-ATPase activity in mTAL. AVP can, depending on Nai, produce this effect by adenylate cyclase activation. The guanonine nucleotide binding protein G-protein might be the site of Na(+)-dependence.

Adenosine Triphosphate↗
PubMed1992

High salt diet down-regulates proximal tubule Na+, K(+)-ATPase activity in Dahl salt-resistant but not in Dahl salt-sensitive rats: evidence of defective dopamine regulation.

We examined the regulation of Na+,K(+)-ATPase activity in proximal tubule segments during a high salt diet in prehypertensive Dahl salt-sensitive and salt-resistant rats. Rats were placed on normal salt or high salt diets (0.9% saline as drinking water). During the normal salt diet, Na+,K(+)-ATPase activity was not different between Dahl salt-sensitive and salt-resistant rats. After 2 days and 10 days on a high salt diet, Na+,K(+)-ATPase activity in Dahl salt-resistant rats significantly decreased when compared to Dahl salt-resistant rats on a normal salt diet (P less than 0.01). The decreased Na+,K(+)-ATPase activity in Dahl salt-resistant rats during a high salt diet was reversed by treatment with an inhibitor of aromatic L-amino acid decarboxylase (dopamine synthesizing enzyme), benserazide. In contrast, Na+,K(+)-ATPase activity did not decrease during the high salt diet and benserazide had no effect on Na+,K(+)-ATPase activity in Dahl salt-sensitive rats. These results indicate that Dahl salt-sensitive rats do not have the capacity to down-regulate the proximal tubule Na+,K(+)-ATPase activity during a high salt diet. Indirect evidence suggests that the regulation of Na+,K(+)-ATPase activity by locally produced dopamine is absent in Dahl salt-sensitive rats.

Animals↗
PubMed1992

Calcium supplementation and thyroid hormone protect against gentamicin-induced inhibition of proximal tubular Na+,K(+)-ATPase activity and other renal functional changes.

Gentamicin can cause proximal tubule necrosis. We have shown that inhibition of PT Na+,K(+)-ATPase activity is rapidly induced by gentamicin. We have now investigated whether manipulations known to attenuate the negative effects of gentamicin on renal excretory capacity, i.e. high calcium intake and L-thyroxine treatment, will also attenuate gentamicin-induced inhibition of Na+,K(+)-ATPase activity and ameliorated signs of proximal tubule damage. Rats were gentamicin- or vehicle-treated for 7 days. Sub-groups were given 4% calcium (Ca) supplements or L-thyroxine 20 micrograms 100 g-1 body weight daily. Gentamicin significantly reduced the glomerular filtration rate and increased the urinary excretion of the proximal tubule lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Gentamicin significantly reduced proximal tubule Na+,K(+)-ATPase activity, measured in single permeabilized proximal tubule segments. Sodium excretion was inversely correlated to proximal tubule Na+,K(+)-ATPase activity. Both calcium and L-thyroxine alleviated all gentamicin-induced side-effects on renal function as well as on proximal tubule Na+,K(+)-ATPase activity. Calcium and L-thyroxine had no significant effect on renal function. L-thyroxine, but not calcium, increased proximal tubule Na+,K(+)-ATPase activity in control rats. Renal cortical tissue gentamicin concentration was not influenced by calcium but was significantly lowered by L-thyroxine. Two procedures which, via different mechanisms, afford protection from gentamicin-induced changes in renal function also give protection from gentamicin-induced inhibition of Na+,K(+)-ATPase activity. This suggests that loss of integrity of the Na+,K(+)-ATPase enzyme contributes to gentamicin-induced nephrotoxicity.

Acetylglucosaminidase↗
PubMed1992

Protein kinase C activity in rat renal proximal tubule cells.

The presence of protein kinase C (PKC) in proximal tubule cells of the rat kidney is established by means of immunodetection and by the demonstration of calcium- and phospholipid-dependent, staurosporine-inhibitable histone phosphorylation. The calcium-dependence of renal PKC is described. Maximal activation of the enzyme (178.2 and 258.8 pmol P1 mg-1 min-1 for cytosol and membrane respectively) was achieved with 5 microM of Ca2+. Phorbol 12, 13 dibutyrate (PDBu) translocated PKC from cytosol to membrane in a dose- and time-dependent fashion, while 4 alpha-phorbol 12,13-didecanoate produced no significant effect on translocation. Cytosolic PKC activity was compared in immature and mature tissues (10- and 40-day-old kidneys). Basal activity was found to be significantly higher (P less than 0.05) in immature cells (272.8 vs. 157.5 pmol Pi mg-1 min-1). PDBu at 10(-6) M for 15 min reduced immunoreactivity in the soluble fraction of both groups, which was accompanied by a significant decrease in kinase activity. We speculate that the high PKC activity in the infant kidney plays a role in cell growth.

Aging↗
PubMed1992

Regulation of glomerular angiotensin II receptor densities in renovascular hypertension: response to reduced sympathetic and vasopressin influence.

The regulation of the density of angiotensin II receptors in renal glomeruli in response to changes in salt intake is altered in Sprague-Dawley rats with renovascular hypertension due to aortic constriction, and in hypertensive salt-sensitive Dahl rats (Sahlgren 1989, Sahlgren & Aperia 1989). This study examines the modulatory role of sympathetic activity and arginine-vasopressin on angiotensin II receptors in hypertensive Sprague-Dawley rats with aortic constriction as well as in normotensive control rats. Denervation of the left kidney caused a 50% increase in the glomerular angiotensin II receptor density in the denervated kidney in both hypertensive rats and normotensive controls. An even more marked increase in glomerular receptor density occurred in both hypertensive rats and controls after blocking the sympathetic nervous system with guanethidine. To block the effects of arginine-vasopressin we used a blocker of the V1-receptors (predominant in vessels) and found an approximately 100% increase in the glomerular receptor density of angiotensin II in rats with aortic constriction. There was no reduction in blood pressure. Thus, on the receptor level the renin-angiotensin system is markedly influenced by the activity of other major pressor systems.

Animals↗
PubMed1992

Intracellular pH regulation in cultured renal proximal tubule cells in different stages of maturation.

This study examines the ontogeny of cellular pH regulation in renal proximal tubule cells (RPTC). RPTC from 8- to 40-day-old Sprague-Dawley rats (RPTC-8 to RPTC-40) were studied after 48 h of primary culture. Intracellular pH (pHi) was measured by quantitative fluorescence microscopy using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Recordings were made under basal conditions and after imposing a cytoplasmic alkalosis and acidosis using 15 mM NH4+ salt. The net recovery rate (dpHi/dt) from intracellular acidosis increases significantly between 10 and 12 days of age from 0.39 +/- 0.04 to 0.54 +/- 0.06 pH units/min (P < 0.05, n = 10 vs. 6). This increase can be completely accounted for by an increase in the rate of amiloride (100 microM)-inhibitable Na(+)-H+ exchange (0.29 +/- 0.04 vs. 0.42 +/- 0.05 pH units/min, P < 0.05, n = 6 vs. 6). The rate of Na(+)-H+ exchange increases similarly in RPTC-10 and RPTC-40 when the transmembrane Na+ gradient is increased by Na+ depleting the cells (48 and 49%, respectively). The amiloride-insensitive recovery is Na+ independent and insensitive to 4-acetamido-4'-isothiocyanostilbene-2-2'-disulfonic acid (SITS, 500 microM) (range 0.08-0.14 pH units/min). The net recovery rate from intracellular alkalosis is significantly lower in RPTC-10 than in RPTC-40 (0.16 +/- 0.02 vs. 0.28 +/- 0.02 pH units/min, P < 0.01, n = 4 vs. 5). SITS (500 microM) inhibits the recovery by 27 +/- 8 and 26 +/- 9%, respectively, whereas amiloride has no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1992

The renal dopamine receptors.

Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and ion fluxes. Dopamine receptors in the brain have been classically divided into D1 and D2 subtypes, based on pharmacological data. However, molecular biology techniques have identified many more dopamine receptor subtypes. Several of the receptors cloned from the brain correspond to the classically described D1 and D2 receptors. Several D1 receptor subtypes have been cloned (D1A, D1B, and D5) and are each coupled to the stimulation of adenylyl cyclase. The D2 receptor has two isoforms, a shorter form, composed of 415 amino acids, is termed the D2short receptor. The long form, called the D2long receptor, is composed of 444 amino acids; both are coupled to the inhibition of adenylyl cyclase. The D3 and D4 receptors are closely related to, but clearly distinct from, the D2 receptor. They have not yet been linked to adenylyl cyclase activity. Outside of the central nervous system, the peripheral dopamine receptors have been classified into the DA1 and DA2 subtypes, on the basis of synaptic localization. The pharmacological properties of DA1 receptors roughly approximate those of D1 and D5 receptors, whereas those of DA2 receptors approximate those of D2 receptors. A renal dopamine receptor with some pharmacological features of the D2 receptor but not linked to adenylyl cyclase has been described in the renal cortex and inner medulla. In the inner medulla, this D2-like receptor, termed DA2k, is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2. Of the cloned dopamine receptors, only the mRNA of the D3 receptor has been reported in the kidney. The DA1 receptor in the kidney is associated with renal vasodilation and an increase in electrolyte excretion. The DA1-related vasodilation and inhibition of electrolyte transport is mediated by cAMP. The role of renal DA2 receptors remains to be clarified. Although DA1 and DA2 receptors may act in concert to decrease transport in the renal proximal convoluted tubule, the overall function of DA2 receptors may be actually the opposite of those noted for DA1 receptors. Dopamine has been postulated to act as an intrarenal natriuretic hormone. Moreover, an aberrant renal dopaminergic system may play a role in the pathogenesis of some forms of hypertension. A decreased renal production of dopamine and/or a defective transduction of the dopamine signal is/are present in some animal models of experimental hypertension as well as in some forms of human essential hypertension.

Humans↗
PubMed1991

Phosphorylation of the catalytic subunit of Na+,K(+)-ATPase inhibits the activity of the enzyme.

We have examined two distinct protein kinases, cAMP-dependent protein kinase and protein kinase C, for their ability to phosphorylate and regulate the activity of three different types of Na+,K(+)-ATPase preparation. cAMP-dependent protein kinase phosphorylated purified shark rectal gland Na+,K(+)-ATPase to a stoichiometry of approximately 1 mol of phosphate per mol of alpha subunit. Protein kinase C phosphorylated purified shark rectal gland Na+,K(+)-ATPase to a stoichiometry of approximately 2 mol of phosphate per mol of alpha subunit. The phosphorylation by each of the kinases was associated with an inhibition of Na+,K(+)-ATPase activity of about 40-50%. These two protein kinases also inhibited the activity of a partially purified preparation of Na+,K(+)-ATPase from rat renal cortex and the activity of Na+,K(+)-ATPase present in preparations of basolateral membrane vesicles from rat renal cortex.

Animals↗
PubMed1991

Phosphorylated Mr 32,000 dopamine- and cAMP-regulated phosphoprotein inhibits Na+,K(+)-ATPase activity in renal tubule cells.

Dopamine inhibits Na+,K(+)-ATPase activity in several renal tubule segments and thereby regulates urinary Na+ excretion. We now show that a phosphopeptide of 31 amino acids, corresponding to residues 8-38 of the protein phosphatase inhibitor DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), mimics the inhibitory action of dopamine on Na+,K(+)-ATPase activity in renal tubule cells from the ascending limb of the loop of Henle. The dephosphorylated form of the peptide is ineffective. The results indicate that dopamine acts through a protein phosphorylation pathway to regulate the activity of an ion pump. In addition, the data suggest that inhibition of protein phosphatase 1 by phophorylated DARPP-32 is a component of the mechanism by which dopamine regulates urinary Na+ excretion.

Amino Acid Sequence↗
PubMed1991

Salt and the newborn kidney.

Renal function differs in term infants from that in adults, with lower glomerular filtration rate (GFR) and reduced proximal tubular reabsorption of sodium (Na) and water: nevertheless, it is adequate for their needs. This is not true of very preterm infants in whom hyponatraemia is common. Animal studies have shown that Na+, K(+)-ATPase and the Na+/K+ exchanger are poorly expressed at birth with rapid postnatal rises. Cell receptors for hormones that influence tubular Na transport are less numerous in the premature infant than later in life: intracellular second messenger systems may also be immature. The low GFR is due to vasoconstriction and may be necessary to prevent water and electrolyte wasting due to tubular overload. The hyponatraemia of prematurity could, in principle, be due either to Na loss or water excess and can be prevented either by giving additional Na or by restricting water intake. Na supplementation causes relative volume expansion (VE), water restriction volume contraction (VC); this is demonstrated by the effect of the two approaches on weight gain and on the levels of vasoactive hormones in the blood. We argue that moderate VE is more physiological than VC, both in attempting to simulate intrauterine conditions and in consideration of the infant's nutritional needs. The much less common complication of hypernatraemia is usually due to abnormal water loss and should be prevented by increasing water intake appropriately. The above applies to well, preterm babies: sick preterm infants are much more variable in their Na and water requirements than well infants of comparable gestation and weight and each needs an individually tailored regimen based on frequent clinical assessment and laboratory measurement.

Biological Transport↗
PubMed1991

Increased renal tubular Na-K-ATPase activity in Milan hypertensive rats in the prehypertensive period.

Milan hypertensive (MSH) rats develop hypertension around the 3rd-4th week of life and exhibit increased Na-pump activity in adulthood. The present study was performed to evaluate whether or not hypertension is preceded by an increase in Na-K-ATPase activity. Total and ouabain-sensitive ATPase activities were studied in single microdissected medullary thick ascending limb of Henle (mTAL) tubules from MHS, Milan normotensive (MNS) and Sprague-Dawley (SD) rats at 22-24, 26-28 and 45-60 days of age. Data are given as mean +/- SEM. Total and Na-K-ATPase activity exhibited a developmental pattern in MHS, MNS and SD rats. At 22-24 days no difference was seen between MHS and MNS animals. At 26-28 days MHS had a higher total and Na-K-ATPase activity than MNS (3031 + 171 vs 2471 + 178 pmol phosphate/mm tubule per hour, P less than 0.05; 2289 + 205 vs 1653 + 151, n = 10, P less than 0.05). At this age there was still no difference in mean arterial blood pressure (88 + 4 vs 86 + 3 mm Hg, n = 15). Adult MHS rats had higher blood pressure (140 + 9 vs 112 + 8 mm Hg, P less than 0.001) and higher total (3544 + 136 vs 2718 + 215 pmol phosphate/mm tubule per hour, n = 10, P less than 0.01) and Na-K-ATPase activity (2670 + 99 vs 1942 + 217 pmol phosphate/mm tubule per hour, n = 10, P less than 0.05) than adult MNS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Renal growth in infancy and childhood--experimental studies of regulatory mechanisms.

During the peri- and early postnatal period, nephrogenesis is completed and kidney growth is accomplished both by cellular proliferation and enlargement. The number of nephrons in a given species is predetermined, whereas cellular growth can be influenced by environmental factors in an age-dependent manner. Unilateral nephrectomy or a high-protein diet stimulates renal growth more in the young than in the adult. Conversely, pyelonephritis inhibits renal growth in infancy but not in adulthood. The relative importance of hyperplasia and hypertrophy for renal growth also changes with renal maturation. The mechanisms behind these developmental changes in regulation of renal growth are largely unknown, but age-dependent changes in the expression of several proto-oncogene products have been demonstrated. These include growth factor receptors as well as components of the intracellular system that transfers the signal from an activated growth factor receptor to the cell nucleus. Studies on rat proximal tubule cells in primary culture might be of great value in expanding our knowledge of growth regulation in the developing kidney. Such studies have already shown that under identical environmental conditions the basal proliferative rate is age dependent, that the proliferative response to growth stimulation changes postnatally, and that this is associated with changes of both the response of the Na+/H(+)-exchanger and the expression of the c-fos proto-oncogene.

Animals↗