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S Sabatini

Publications and source records attributed to S Sabatini.

121 records · Page 7Linked to original sources
PubMed1980

Effect of quinidine on Na, H+, and water transport by the turtle and toad bladders.

The effect of quinidine on Na and H+ transport by the turtle bladder and water transport by the toad bladder was examined. Quinidine inhibited the short-circuit current and the potential difference in a dose-dependent fashion. The effect of quinidine on the short-circuit was not dependent on extracellular calcium concentration and was not reversible with removal of the drug. Quinidine inhibited H+ secretion in a dose-dependent fashion. The effect of quinidine on H+ secretion also was not dependent on extracellular calcium concentration and was not reversible, either with removal of the drug or with stimulation of H+ secretion with 5% CO2. The effect of quinidine on Na or H+ transport could not be elicited by an equivalent dose of tetracaine, suggesting that the inhibitory effect of quinidine is not dependent on its anesthetic properties. Quinidine also inhibited vasopressin and cyclic AMP stimulated water flow in the toad bladder. Quinidine did not alter calcium uptake by the turtle bladder but increased calcium efflux by the turtle and toad bladders. These observations suggest that a rise in cytosolic calcium is responsible for the inhibitory effect of quinidine on Na, H+, and water transport.

Animals↗
PubMed1980

Distal acidification defect induced by phosphate deprivation.

The effect of phosphate deprivation on urinary acidification was investigated in rats fed a phosphate-deficient diet and in control rats fed the same diet supplemented with phosphate. Phosphate-deprived animals developed hypophosphatemia, hypercalcemia, and hypophosphaturia, but failed to develop hyperchloremic metabolic acidosis following 30 or 60 days of phosphate deprivation. Baseline urine pH was significantly higher in phosphate-deprived rats than in controls, but baseline urine HCO3 excretion was not significantly different between the two groups. The pattern of HCO3 reabsorption in phosphate-deprived rats was identical to that of controls at both low and high plasma HCO3 levels. During chronic NH4Cl administration, both 30- and 60-day phosphate-deprived rats had a sigificantly higher minimal urine pH and lower titratable acid and net acid excretion than seen in controls. NH4 excretion was significantly lower than controls in the 60-day phosphate-deprived rats only. During Na2SO4 administration the minimal urine pH was significantly lower in controls than in phosphate-deprived rats, but there was overlap of urine pH values. At comparable levels of urine pH, NH4 excretion was significantly lower in phosphate-deprived rats than in controls. Phosphate-deprived rats were able to raise urine-blood CO2 pressure to the same levels as controls during both HCO3 loading and Tris buffer administration. Phosphate-deprived rats had greater extrarenal buffering capacity than controls as evidenced by a lower decline in blood pH and HCO3 during HCl infusion in phosphate-deprived rats. These data demonstrate that phosphate deprivation is associated with distal acidification defect, impaired NH3 excretion, and increased extrarenal buffering capacity. The increased availability of buffer in phosphate deprivation may play an important role in acid-base homeostasis in this condition.

Acid-Base Imbalance↗
PubMed1980

Cholinergic inhibition of urinary acidification by the turtle bladder.

The effect of carbachol on urinary acidification by the turtle bladder in vitro was studied. Carbachol inhibited urinary acidification in a dose-dependent fashion, with half maximal inhibition occurring at 4.5 x 10(-5) M. The effect of carbachol on urinary acidification could be totally prevented by atropine, indicating that the inhibition is mediated through a muscarinic receptor. Carbachol inhibited hydrogen ion secretion by decreasing the active proton conductance and not by altering the proton motive force. Carbachol failed to increase passive loss of hydrogen ion from the mucosa. Carbachol increased calcium uptake by the turtle bladder; this increase in calcium uptake could be prevented by pretreatment with atropine, pentobarbital, or lanthanum. Pentobarbital or lanthanum blunted the inhibitory effect of carbachol on hydrogen ion secretion. In the presence of low extracellular calcium (0.2 mM), carbachol failed to increase calcium uptake but caused a significant inhibition of hydrogen ion secretion. In the presence of normal calcium concentration, carbachol caused a significant efflux of calcium. These data demonstrate that carbachol inhibits urinary acidification and suggest that the mechanism of this inhibition may be related, at least in part, to changes in cytosolic calcium.

Animals↗
PubMed1980

Cholinergic modulation of water transport in the toad bladder.

The effect of carbachol on water transport by the toad bladder was studied. Carbachol caused a small increase in base-line water flow and inhibited, partially, vasopressin- (AVP) or cyclic AMP-stimulated water flow. The effect of carbachol on base-line or AVP-stimulated water flow was totally prevented by atropine, indicating that the effect of cabachol on water transport is mediated through a muscarinic receptor. Carbachol caused a significant increase in 45Ca uptake by toad bladder; this increase in calcium uptake could be prevented by atropine, pentobarbital, or lanthanum. The effect of carbachol on base-line and AVP-stimulated water flow was also prevented by pentobarbital or lanthanum, suggesting that the effect of carbachol is mediated, at least in part, by an increase in calcium uptake. The ionophore A-23187, an agent that increased 45Ca uptake, also enhanced base-line water flow and inhibited AVP-stimulated water flow. The effects of carbachol and the ionophore A-23187 on base-line water flow, AVP-stimulated water flow, and on calcium uptake were not additive, suggesting that both agents alter water transport by a similar mechanism. These data demonstrate that carbachol stimulates base-line water transport and inhibits AVP-stimulated water transport. They suggest that the alteration in water transport induced by carbachol is related to an increase in calcium uptake.

Animals↗
PubMed1980

Parathyroid hormone and extrarenal acid buffering.

The role of parathyroid hormone (PTH) on the extrarenal buffering of an acid load was examined during HCl infusion (5 meq x kg-1 x h-1) to bilaterally nephrectomized rats. Thyroparathyroidectomized (TPTX) rats replaced with PTH had significantly higher blood pH and HCO3 values than TPTX rats not infused with PTH. Administration of EDTA, in a dose shown to release PTH, was associated with a significant increase in buffering capacity in intact but not in TPTX rats. Colchicine, given in a dose capable of stimulating PTH release, was also associated with enhanced buffering capacity in intact but not in TPTX rats. In TPTX rats infused with acetazolamide and PTH, the hormone failed to enhance extrarenal buffering of an acid load. Animals with chronic renal failure, induced by infarction of the kidney, also had an enhanced capacity to buffer an acid load. This enhanced buffering capacity in chronic renal failure was abolished by TPTX. Acute renal failure induced by bilateral ureteral ligation was also associated with increased buffering only in the presence of parathyroid glands. These data demonstrated that PTH, from either an exogenous or endogenous source, enhances extrarenal buffering capacity of an acid load. Chronic and acute renal failure are associated with increased buffering capacity, which is dependent on the presence of parathyroid glands. The data suggest that this effect is mediated through carbonic anhydrase.

Acid-Base Equilibrium↗
PubMed1980

[Monoamine oxidase inhibitors. I. Synthesis of N-cyclopropyltryptamines].

The synthesis of two new N-cyclopropyltryptamines is described. By treating 5,6-dimethoxyindole with oxalyl chloride and N-benzylcyclopropylamine, N-benzyl-N-cyclopropyl-5,6-dimethoxyindole-3-glyoxalamide is obtained. The reduction of this compound by LiAlH4, gives N-benzyl-N-cyclopropyl-5,6-dimethoxytryptamine, which is hydrogenated to N-cyclopropyl-5,6-dimethoxytryptamine. Similarly N-cyclopropyl-6,7-dimethoxytryptamine is prepared. Preliminary results indicate a different specificity of the inhibitors used on mitochondrial and bovine plasma enzyme (monoamine oxidase) attributable to the position of the methoxy groups.

5-Methoxytryptamine↗
PubMed1980

Inhibition of H+ secretion in the turtle bladder by colchicine and vinblastine.

In order to investigate a possible role of the microtubules in urinary acidification we measured H+ secretion by the turtle bladder in vitro before and after addition of either colchicine or vinblastine to the serosal phase. Both colchicine and vinblastine inhibited H+ secretion in a dose-dependent fashion; in the control hemibladders H+ secretion remained unchanged. The half-maximal inhibition of H+ secretion occurred at 5.2 x 10(-5) M for colchicine and 7.2 x 10(-6)M for vinblastine. The inhibitory effect of colchicine and vinblastine on H+ secretion was maximal at 10(-4)M and 5 x 10(-4)M, respectively. At these concentrations these compounds failed to alter SCC and resistance. The inhibition of H+ secretion by colchicine or vinblastine increased with time of exposure to the drugs. The effect of colchicine or vinblastine on H+ secretion was not reversible with removal of the drug or with addition of 5% CO2 in the serosal phase. Lumicolchicine, an isomer of colchicine devoid of capacity to interact with microtubules, failed to alter the rate of H+ secretion, suggesting that the observed effect of colchicine on H+ secretion was the result of disruption of microtubule function and not the consequence of nonspecific effect of the drug. These data provide evidence for a role of microtubules in urinary acidification by the turtle bladder in vitro, but an effect of these drugs on membrane-bound tubulin cannot be excluded.

Animals↗
PubMed1979

Functional characterization of drug-induced experimental papillary necrosis.

The functional expression of papillary necrosis was investigated with a model of drug-induced papillary necrosis. Bromoethylamine hydrobromide (BEA) administration to rats uniformly resulted in the development of papillary necrosis. All studies were performed 24 hours after BEA administration with the exception of the electrolyte balance studies, which were performed during the 72 hours after the induction of papillary necrosis. GFR was not different between BEA-treated and sham rats. BEA-treated rats had a significantly lower maximal urine osmolality and free water reabsorption than did sham rats. Renal tissue concentrations of sodium, potassium, and water were not different between BEA-treated and sham rats. During water diuresis, free water clearance was not significantly different between the two groups. During sodium bicarbonate administration, maximal bicarbonate reabsorption and urine-blood Pco2 gradient (at comparable urine bicarbonate concentrations) were not significantly different between the two groups. During sodium sulfate infusion, there was no difference in minimum urine pH, ammonium excretion, and net acid excretion between chronically acidotic BEA-injected and sham rats. In rats on "zero" sodium intake, BEA administration resulted in a significant increase in urine flow and sodium excretion, whereas sham rats remained in sodium balance. In rats with restriction of both sodium and chloride, BEA administration resulted in a significant wastage of sodium, chloride, and calcium. There was no difference in potassium excretion between BEA-treated and sham rats during hydropenia, bicarbonate administration, sodium sulfate infusion, or ingestion of a normal potassium diet. When potassium intake was restricted to "zero," BEA-treated rats developed potassium wastage; when potassium intake was increased to 21 mEq/day, BEA-treated rats had a significantly lower potassium excretion than did sham rats. These findings may result from alterations in collecting duct transport, but damage to deep medullary structures may also contribute.

Animals↗
PubMedDate not supplied

Age-related changes in renal function, membrane protein metabolism, and Na,K-ATPase activity and abundance in hypokalemic F344 x BNF(1) rats.

BACKGROUND: Potassium depletion is a common electrolyte abnormality in elderly humans, usually as a consequence of diuretic use or poor oral intake. Hypokalemia is associated with a number of changes in renal function and an increase in some renal membrane transporters; its growth-promoting effect in young animals is well known. With aging, the renal adaptation to a number of challenges is often diminished. We hypothesized that aging is related to decreases in renal function, renal membrane protein metabolism, as well as Na, K-ATPase protein abundance and activity in both control animals as well as in those with potassium depletion. OBJECTIVE: We examined the effects of dietary-induced hypokalemia in true-aged nonobese rats (30 months old) on renal function, cortical brush border membrane (BBM) and basolateral membrane (BLM) protein metabolism, and Na,K-ATPase protein abundance and activity. We compared the results obtained to those seen in their 4-month-old counterparts similarly treated. METHODS: Young (4-month-old) and senescent (30-month-old) male Fisher 344 x Brown-Norway F(1) rats (F344 x BNF(1)) were fed either a normal or potassium-deficient diet for 7 days. At 24 h, the U-(14)C-leucine incorporation was measured for determination of protein metabolism in renal BBM and BLM. Cortical BLM vesicle and microdissected proximal convoluted tubule (PCT) Na, K-ATPase activities were determined along with Western blot analysis of the cortical BLM alpha(1) subunit of Na,K-ATPase. Metabolic and renal function parameters were also examined. RESULTS: Hypokalemia caused hyperbicarbonatemia, hyperglycemia, and azotemia, but only in the senescent animals. The aged control rats had a higher basal level of urine volume, ammonium excretion, and fractional excretion of chloride. By contrast, aging in the F344 x BNF(1) rats was associated with a decrease in plasma aldosterone (by 35%) and phosphate (by 40%) levels as compared with their young controls. Hypokalemia resulted in a significant reduction of plasma aldosterone and a rise in muscle sodium concentration in both age groups; it significantly increased renal BBM and BLM protein concentrations in the young group, while these parameters remained unchanged in the senescent rats. The aged potassium-depleted animals showed a 14% decrease in BBM protein biosynthesis, but there were no changes in the young hypokalemic rats. Both potassium-depleted elderly and young rats had a significant reduction (by 33%) in BLM protein biosynthesis. Hypokalemia significantly increased the Na, K-ATPase activity in both cortical BLM vesicles and in microdissected PCT. The percentage increase in microdissected PCT segments (Na,K-ATPase activity) in elderly potassium-depleted animals was significantly less than that seen in hypokalemic young ones. Aging, per se, was associated with decreased basal microdissected PCT Na,K-ATPase activity in control animals. Hypokalemia had no effect on cortical BLM alpha(1) subunit Na, K-ATPase protein abundance in either age group. CONCLUSIONS: The present study provides the first evidence in nonobese aged rats as to the metabolic parameters, renal function, renal cortical membrane protein metabolism, and transporter Na,K-ATPase activity and abundance during potassium depletion. The aged nonobese F344 x BNF(1) rats responded differently from their young nonobese counterparts following potassium depletion. These differences may contribute substantially to the effects often encountered in elderly humans receiving diuretics or having a poor dietary potassium intake.

Age Factors↗
PubMedDate not supplied

Anemia and cardiovascular complications: iron and EPO impact.

Management of end-stage renal disease (ESRD) has been revolutionized by the advent of erythropoietin replacement. We briefly review its characteristics and clinical use. Also emphasized is the importance of iron deficiency in limiting the clinical response to erythropoietin therapy. Iron-replacement therapy in ESRD patients is briefly discussed.

Anemia↗
PubMedDate not supplied

Renal Na+, K+-ATPase in SHR: studies of activity and gene expression.

The mechanism by which increased dietary intake of calcium reduces blood pressure in the spontaneously hypertensive rat is unknown. The present studies were designed to determine if there were alterations in the activity of the major membrane ion translocating pump, sodium, potassium-ATPase (NKA), in the kidneys of hypertensive rats and whether increased dietary calcium intake affected the activity of this enzyme. Fifteen-week old SHR's were found to have lower total ATPase activity in microsomal preparations from the kidney than age matched Wistar-Kyoto animals. Both the ouabain-sensitive component (NKA) and the ouabain-insensitive component were lower in SHR. Increasing dietary calcium intake from 1% to 3% elevated both components of the ATPase activity in SHR, but was without effect in WKY. Measurement of membrane phospholipid composition suggested that altered phospholipid composition did not account for the reduced ATPase activity observed, but indicated a reduced density of ATPase in SHR. A technique has been devised for qualitative and quantitative analysis of Na, K-ATPase alpha isoforms using RT-PCR. This technique reveals that the alpha 1 isoform is the sole catalytic isoform present in the nephron. Accurate and precise quantification of the amount of gene expression in individual nephron segments is reported and will be applied to determine whether dietary calcium influences blood pressure by a mechanism which alters nephron NKA gene expression.

Animals↗