PubMed Health⌕ Search

Biomedical subjects

W N Suki

Publications and source records attributed to W N Suki.

At least 19 recordsLinked to original sources
PubMed1992

Evidence for a fourth rat isoform of the plasma membrane calcium pump in the kidney.

This study was conducted to identify plasma membrane Ca(2+)-transporting ATPases present in rat kidney. Characterization of the cDNAs of the plasma membrane Ca(2+)-ATPases revealed a family of proteins with regions of highly conserved amino acid sequence. To examine the extent of the diversity of rat renal plasma membrane Ca(2+)-ATPases, we used the polymerase chain reaction to detect additional gene products in rat kidney mRNA that shared these conserved regions. Sequences corresponding to three previously known rat plasma membrane Ca(2+)-ATPases were obtained. In addition, we found sequence corresponding to a new putative plasma membrane Ca(2+)-ATPase. Our results demonstrate that the rat kidney contains at least four different plasma membrane Ca(2+)-ATPases and the complexity of this multigene family is greater than previously thought.

Amino Acid Sequence↗
PubMed1992

Reconstitution and partial purification of calcium transport activity from rat kidney cortex.

An ATP-dependent Ca2+ uptake system from rat renal cortical basolateral membranes was solubilized with Triton X-100 and reconstituted into liposomes with lecithin. In the presence of Mg2+, Ca2+ uptake in the reconstituted vesicles was time and ATP dependent and was inhibited by vanadate. Ca2+ uptake in basolateral membrane vesicles depleted of endogenous calmodulin was enhanced by exogenous calmodulin and depressed by R-24571. This sensitivity to calmodulin and R-24571 was lost upon reconstitution in the presence and absence of leupeptin. Vesicles containing Ca2+ uptake activity were separated by gradient centrifugation after Ca2+ was taken up and accumulated as calcium phosphate in the vesicles. This resulted in Ca2+ uptake activity that was enriched 25 times. However, Ca(2+)-dependent adenosinetriphosphatase (ATPase) activity was not enriched significantly. This Ca(2+)-ATPase had two kinetic forms for Ca2+: one was a high-affinity low-capacity form; the other had a low affinity and high capacity. The Ca(2+)-ATPase activity also had two kinetic forms for ATP. All kinetic forms were inhibited by Mg2+. Vanadate, calmodulin, and R-24571 had no effects on Ca(2+)-ATPase activity. A protein doublet of Ca(2+)-dependent hydroxylamine-sensitive phosphorylated intermediates was demonstrated at 125 and 136 kDa in the purified vesicles. This doublet was not altered by addition of leupeptin throughout the purification.

Adenosine Triphosphate↗
PubMed1991

TMB-8 prevents the hydroosmotic response to ADH in rabbit cortical collecting tubules.

Both AVP and dDAVP effect a transient increase in cytosolic free calcium (iCa2+) in cortical collecting tubule (CCT) cells. To investigate the physiological role of this increase in iCa2+, we examined the effect of TMB-8, a putative inhibitor of iCa2+ release, on the initial and sustained phase of AVP- and dDAVP-stimulated water permeability (Pf) in isolated, perfused CCTs. Pretreatment of tubules with TMB-8, 50 microM, suppressed the increase in osmotic water permeability (Pf) induced by 10 microU/ml AVP and dDAVP, but had no effect on the sustained phase of the response. When increased to 100 microM. TMB-8 inhibited the sustained phase of AVP action. A similar pattern was observed on AVP-stimulated adenyly cyclase activity in rabbit renal membranes. Pretreatment of tubules with 50 microM TMB-8 attenuated the initial increase in Pf in response to cholera toxin but not to 8-Br-cAMP or forskolin. There was no effect of this concentration of TMB-8 on the sustained phase of these agonists. These studies suggest that, in lower concentrations, TMB-8 inhibits the mobilization of iCa2+, which is important for the interaction of Gs with the catalytic unit of adenylyl cyclase and the initial increase in AVP-stimulated Pf. In higher concentrations, TMB-8 inhibits adenylyl cyclase activity directly.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Role of Ca2+/H+ antiporter in the kidney.

Three different mechanisms for H+ transport mediated by Ca2+ have been reported. First is an ATP-dependent Ca2+/H+ antiporter which is catalyzed by (Ca2+ + Mg2+)-ATPase in plasma membrane. Second is a compensatory Ca2+ movement associated with an ATP-dependent H+ pump catalyzed by H(+)-ATPase in endosome. Third is a mitochondrial Ca2+ movement driven by an electrophoretic H+ driving force. All these processes must play a critical role on transfering messages between Ca2+ and H+. Data indicate that an ATP-dependent Ca2+ pump is an electroneutral Ca2+/H+ antiporter in renal tubular cells as well as in other nonrenal cells. The existence of this process is compatible with the physiological phenomena of Ca2+ and H+ transport in renal tubules, although we still lack direct evidence to comprehend the role of the Ca2+/H+ pump in the kidney.

Acids↗
PubMed1990

Clonidine inhibits fluid absorption in the rabbit proximal convoluted renal tubule.

Previous studies have shown that norepinephrine (NE) and the beta-adrenoceptor agonist, isoproterenol (I), enhance fluid absorption (JV) in isolated, perfused proximal convoluted tubule segments (PCT). Pretreatment of PCT with the beta-adrenoceptor antagonist, propranolol, inhibited the action of NE and produced a significant decline in JV, suggesting modulation of JV by both alpha- and beta-adrenoceptors. The present studies further characterize the alpha-adrenoceptor control of JV in isolated perfused PCT using specific agonists and antagonists. Basal JV declined significantly with the addition of the alpha 2-adrenoceptor agonist, clonidine (10(-4) M), to the bath; however, it was unchanged with the addition of the alpha 1-adrenoceptor agonist, methoxamine (10(-6) or 10(-4) M). With the addition of 10(-6) M isoproterenol JV increased significantly, and returned to control values with the subsequent addition of clonidine (10(-6) or 10(-4) M). Pretreatment of PCT with the alpha 2-adrenoceptor antagonist, yohimbine (10(-5) M), or with pertussis toxin (100 ng/ml) did not interfere with the stimulation of JV by isoproterenol, but abolished the inhibition of isoproterenol-stimulated JV by clonidine. Thus, clonidine inhibits JV in PCT via an alpha 2-adrenoceptor. This effect is mediated by a pertussis toxin inhibitable GTP-binding protein, but not one that is coupled to adenylyl cyclase.

Adenylate Cyclase Toxin↗
PubMed1990

AVP and dDAVP in rabbit cortical collecting tubule: a comparative time-course study.

The V2-selective analogue of arginine vasopressin (AVP), dDAVP, has been used to distinguish between the effects of V1- and V2-receptor activation by AVP in different cell types of the kidney. Based on studies showing different effects of AVP and dDAVP on prostaglandin secretion, and also on cytosolic Ca2+, we designed a comparative time-course study of both agonists on rabbit microdissected cortical collecting tubules (CCT) microperfused in vitro at 38 degrees C. Plots of the effects of AVP (10 microU/ml or 2.2 x 10(-11) M and 100 microU/ml or 2.2 x 10(-10) M) and dDAVP (10 microU/ml or 0.8 x 10(-11) M) on osmotic water permeability (Pf) at comparable antidiuretic activities, revealed an increase of Pf that was maintained for as long as 170 min of hormone exposure. Also the magnitude of increase in Pf and the time required to achieve the more sustained phase of response were comparable, with no significant difference between the two agonists. These results clearly demonstrate a stable response of rabbit CCT to AVP and dDAVP at physiological temperature, and they reveal no evidence for a difference between the native hormone AVP and its V2 selective analogue on the net hydrosmotic response of the CCT.

Animals↗
PubMed1990

Calcium and the kidney--from stones to molecules.

Shortly after the introduction of the thiazide diuretics it was noted that they lower the excretion of Ca2+ in the urine, enough so that they were introduced for the therapy of hypercalciuria in calcareous stone formers. This observation prompted us to begin a series of investigations designed to better understand the handling of Ca2+ by the kidney in general, and the effects of diuretics on Ca2+ transport in particular. Since it was already known that the excretion of Ca2+ followed closely the excretion of Na+ we postulated that the effects of diuretics are related to the shrinkage of extracellular (ECF) volume which signals the kidney to enhance filtrate absorption particularly in the proximal tubule. This we supported with studies showing that calcium excretion will return to the original elevated level, inspite of continued administration of the diuretic, if a high salt intake were allowed. We also showed the opposite, namely that hypercalciuria can be produced by mineralocorticoid administration if liberal salt intake were allowed, and is prevented by salt restriction. This latter observation antedated the clinical observation that primary aldosteronism is accompanied by hypercalciuria. These studies clearly showed the importance of ECF volume in determining urinary excretion of Ca2+. The site of action in the nephron of volume changes was thought to be the proximal convoluted tubule. Volume expansion had already been shown to depress proximal tubular absorption of Ca2+. We carried out studies using in situ micropuncture and demonstrated that ECF volume depletion caused by thiazide diuretics results in enhanced absorption in the proximal tubule confirming the suspicion that changes in ECF volume were translated into reciprocal changes in proximal tubular absorption. Meanwhile we showed that a different group of diuretics, the high-ceiling diuretics, unlike the thiazides produce a major increase in Ca2+ excretion suggesting that they exert their effects at a different site in the nephron, namely the loop of Henle. These and many other studies dictated that we examine more directly the handling of Ca2+ by the kidney, and for that purpose we employed the technic of in vitro microperfusion of isolated renal tubule segments. In the S2 segment of the proximal convoluted tubule we were able to show that Ca2+ absorption was entirely passive, following the electrochemical gradient for calcium present in this segment (luminal PD positive, tubular fluid [Ca2+] greater than plasma [Ca2+]).(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Transport↗
PubMed1989

Reversal of left ventricular dysfunction after renal transplantation.

We report the cases of four patients with end-stage renal disease and New York Heart Association class III or IV heart failure of nonischemic origin as documented by coronary angiography. Because of left ventricular dysfunction (left ventricular end-diastolic pressure, 23 to 30 mm Hg; ejection fraction, 20% to 35%), all four patients were initially considered poor surgical candidates for renal transplantation. These same four patients became asymptomatic, however, with markedly improved cardiac function (ejection fraction, 43% to 69%) detected as early as 6 and 14 days after renal engraftment. Therefore, there exists a subset of patients with end-stage renal disease in whom congestive heart failure should not be considered a contraindication to renal transplantation. We conclude that some dialysis-dependent patients who manifest symptomatic heart failure of nonischemic origin have a reversible cardiomyopathy and should not be denied renal transplantation.

Adult↗
PubMed1989

Effects of uninephrectomy and high protein feeding in cyclosporine nephropathy.

Using a recently described rodent model of chronic cyclosporine nephropathy (CCN), the effects of uninephrectomy (UNx) and high protein feeding on the development of CCN were studied. After 28 days of i.p. cyclosporine (Cs; 25 mg/kg/day) in UNx and sham nephrectomized (SNx) rats, the single kidney GFR was higher in UNx animals (0.55 +/- 0.09 vs. 0.29 +/- 0.05 ml/min, P less than 0.04) as was RPF (3.05 +/- 0.46 vs. 1.45 +/- 0.37 ml/min, P less than 0.04). Morphometric evaluation of the chronic tubulointerstitial lesion (TI) demonstrated lower scores and relative protection in the UNx group (16.48 +/- 3.52 vs. 64.76 +/- 18.30, P less than 0.01). In separate groups of rats undergoing UNx or SNx and subsequent treatment with Cs, dry kidney weights confirmed that compensatory renal hypertrophy was present in UNx animals. The modulating effect of dietary protein on the lesion of CCN was studied in UNx rats fed a 5% or 60% protein diet during the period of Cs treatment. At the end of the study period animals fed the high protein diet demonstrated a higher RPF (3.19 +/- 0.58 vs. 1.58 +/- 0.29 ml/min, P less than 0.04), higher GFR (0.55 +/- 0.07 vs. 0.35 +/- 0.04 ml/min, P less than 0.05) and lower TI score (64.45 +/- 17.35 vs. 130.32 +/- 23.48, P less than 0.04) when compared with animals consuming a low protein diet. We conclude that the relative renal vasodilation induced by partial ablation of renal mass and high protein feeding affords some protection against the development of CCN.

Animals↗
PubMed1989

Renal hemodynamic consequences of angiotensin-converting enzyme inhibition in congestive heart failure.

Angiotensin-converting enzyme (ACE) inhibitors are of benefit in the management of heart failure. In some studies in patients with heart failure, a decline in renal function occurred more frequently in patients treated with enalapril maleate, a longer-acting agent, than in those treated with captopril, a shorter-acting drug. Patients experiencing a decline in renal function had a number of predisposing hormonal and hemodynamic factors. In one report, these factors included an initial fall in blood pressure that was sustained, lower cardiac output, and a relatively high fixed dose of enalapril that contributed to renal impairment. In a second study, the decline in renal function was most severe in patients with a lower systemic arterial pressure in whom glomerular filtration may have been dependent on angiotensin II. In a third study, intravascular volume depletion and an activated renin-angiotensin system led to reduced renal function. Reduction of angiotensin II level in plasma and tissues by ACE inhibitors decreases systemic vascular resistance and efferent arteriolar tone, which tends to decrease glomerular filtration rate. If compensatory increases in cardiac output are inadequate or preexisting renal impairment or volume depletion is present, renal function will deteriorate. Long-acting ACE inhibitors prolong the decreased efferent arteriolar tone and may compromise cardiac muscle response to catecholamines. The use of shorter-acting agents in patients who exhibit deterioration in renal function may be preferable.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients.

Hyperlipidemia, particularly hypercholesterolemia, occurs in cardiac transplant recipients both as a preexisting condition and as a consequence of immunosuppressive therapy. Lovastatin (Mevacor) has emerged as an agent that may effectively manage this condition. Few serious side effects of this drug have been observed. We describe two cardiac transplant recipients treated with lovastatin in conjunction with their other medications, including cyclosporine, who developed acute renal failure and rhabdomyolysis. Resolution of muscle damage followed discontinuation of cyclosporine and lovastatin therapy. We postulate that hepatic dysfunction secondary to cyclosporine predisposed these patients to lovastatin-induced muscle damage. Use of this drug in cardiac and other organ transplant recipients should be accompanied by close surveillance of creatine kinase, hepatic transaminases, and cyclosporine levels.

Acute Kidney Injury↗
PubMed1988

The mechanism of hypercalciuria in streptozotocin-induced diabetic rats.

Metabolic studies were performed in streptozotocin-induced diabetic (D) rats and normal control (C) rats to assess the role of hyperphagia in the hypercalciuria of diabetes. Urinary calcium excretion (UCaV) was significantly higher in D v C rats fed ad libitum. When D rats were pair-fed (calorie and mineral restriction) with C rats, UCaV declined but remained significantly higher than in C rats. When D rats were allowed their usual increased calorie intake but restricted to C rat mineral consumption, UCaV remained elevated. These findings suggested a tubular reabsorptive defect. In vivo microinjection studies were then performed to identify the site(s) of the tubular reabsorptive defect. Using 1.0 mmol/L Ca in the injectate, 45Ca recovery in the urine (CaR%) was significantly higher in D rats after intratubular injections into early and late proximal tubules and late distal but not early distal tubules. An additional load-dependent defect was revealed in the terminal nephron when the Ca concentration of the injectate was increased to 1.8 mmol/L. After early distal injection, CaR% was significantly increased in D v C rats. Infusion of PTH into thyroparathyroidectomized C and D rats enhanced Ca absorption to a similar degree but did not correct the reabsorptive defect in D rats. These results argue against a lack of end-organ responsiveness to PTH in diabetes or a low serum PTH level as the cause of the hypercalciuria. We conclude that hyperphagia contributes to the hypercalciuria of diabetes in the absence of increased Ca intake. Also, two tubular reabsorptive defects exist: one in the loop of Henle; the other, load-dependent in the terminal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1988

Measurement of GFR with non-radioisotopic radio contrast agents.

The clearance of creatinine has been shown to overestimate GFR in patients with renal disease and in kidney transplant recipients. Alternate means for measuring GFR involve the use of constant infusion and, frequently, of radioisotopes. We report herein the measurement of GFR with the use of a radiocontrast agent (diatrizoate meglumine) injected subcutaneously with a small amount of epinephrine (0.05 ml of 1:1000). The concentrations of this marker of glomerular filtration in blood and in urine were measured with high-performance liquid chromatography. The results demonstrate that with this method of administration stable blood levels are observed for at least three hours. Furthermore, creatinine clearance overestimated GFR by 50% and by 68% in patients with renal disease and in renal transplant recipients, respectively. This method offers several advantages: 1) the use of commonly available and inexpensive materials; 2) obviates the need for the use of constant infusions; and 3) avoids the use of radioisotopes.

Adult↗