Search PubMed⌕ Search

Biomedical subjects

S Klahr

Publications and source records attributed to S Klahr.

At least 235 records · Page 13Linked to original sources
PubMed1978

Cholinergic agents inhibit sodium transport across the isolated toad bladder.

Acetylcholine and carbamylcholine (carbachol) inhibited sodium transport across the toad bladder. This effect was blocked by atropine. Carbachol increased the uptake of 45Ca by isolated toad bladder epithelial cells. This increased 45Ca uptake was blocked by atropine, pentobarbital, or lanthanum chloride. The inhibitory effect of cholinergic agents on sodium transport was dependent on external calcium concentration and was abolished by decreasing external calcium from 2 to 0.2 mM or by agents (pentobarbital, lanthanum chloride) which prevent the movement of calcium into cells. Carbachol increased modestly, but significantly, the levels of cyclic GMP in isolated toad bladder epithelial cells. This effect was blocked by atropine. Whether the decrease in sodium transport produced by cholinergic agents is the result of increased intracytoplasmic calcium levels, increased cyclic GMP levels, or a combination of both remains to be established.

Acetylcholine↗
PubMed1978

Selective uptake of the synthetic amino terminal fragment of bovine parathyroid hormone by isolated perfused bone.

Studies from our laboratory have shown that the metabolic clearance rate of carboxy terminal immunoreactive parathyroid hormone (i-PTH) can be accounted for by extraction of i-PTH by liver and kidney. In contrast, there was no demonstrable hepatic uptake of the synthetic amino terminal bovine PTH fragment (syn b-PTH 1-34) and the kidney accounted for only 45% of the metabolic clearance rate of amino terminal i-PTH. This suggested that another major site, presumably bone, played a role in the metabolism of syn b-PTH 1-34. Extraction of i-PTH by isolated perfused bone was studied during infusion of purified bovine PTH (b-PTH) 1-84 or syn b-PTH 1-34. In five studies during infusion of syn b-PTH 1-34 the arteriovenous difference for i-PTH across bone was 36%. In contrast, no significant uptake of carboxy terminal i-PTH was observed in nine studies during infusion of b-PTH 1-84. In addition, when H(2)O(2)-oxidized (biologically inactive) syn b-PTH 1-34 was used no arteriovenous difference was observed. These findings correlated with the ability of these PTH preparations to stimulate cyclic AMP production by the perfused bone. Syn b-PTH 1-34 increased cyclic AMP production at perfusate PTH concentrations of 1-5 ng/ml, whereas b-PTH 1-84 evoked only a minimal response at concentrations of 10-20 ng/ml. We conclude that bone is a major site of metabolism of the amino terminal PTH fragment, syn b-PTH 1-34. In addition, these data suggest that cleavage of the intact hormone, with the production of amino terminal PTH fragments by peripheral organs (liver and kidney), may play a major role in the regulation of PTH effects on bone.

Animals↗
PubMed1978

Deep nephron function after release of acute unilateral ureteral obstruction in the young rat.

The effects of acute unilateral ureteral obstruction (UUO) of 18 h duration on deep nephron function was evaluated in 14 weanling rats with the technique of micropuncture. After release of UUO, 3.4 +/- 0.66% (SE) of the filtered water remained at the tip of the collecting duct nearly fivefold greater than in controls (0.75 +/- 0.10%). Similar differences were seen in fractional sodium that remained at this site. The ratio of tubular fluid osmolality to that of plasma was also reduced in the UUO group (1.53 +/- 0.06 vs. 4.60 +/- 0.26 in controls, P less than 0.001). Single nephron glomerular filtration rate of cortical and deep nephrons was significantly less (P less than 0.001) after release of UUO. Although the percentage of filtering nephrons was significantly reduced in both nephron populations, the decline in glomerular filtration rate was greater in cortical than in juxtamedullary nephrons (cortical:juxtamedullary nephrons = 27.6 +/- 4.5% vs. 53.3 +/- 5.2% in controls, P less than 0.005) which suggests that single nephron glomerular filtration rate is redistributed to deep nephrons after release of UUO. In contrast to cortical nephrons, the amount of tubular fluid which remains near the bend of the loop of Henle of deep nephrons was greater after release of UUO. This appeared to be the result of a decrease in the reabsorption of both water (tubular fluid:plasma inulin = 2.41 +/- 0.16 vs. 7.94 +/- 0.69 in controls, P less than 0.001) and sodium (52.3 +/- 4% vs. 40.7 +/- 2.9% of the filtered sodium in controls, P less than 0.02). It is suggested that this altered reabsorption occurs along both the proximal tubule and descending limb of the loop of Henle of juxtamedullary nephrons. Inner medullary plasma flow (IMPF), as measured with the [125I]albumin-accumulation technique, was significantly depressed before release of UUO, but exceeded control values 90 min postrelease. Such changes imply that the filtration fraction of deep nephrons is decreased and that physical factors in the proximal tubular reabsorption of sodium have been altered. When papillary solute content was measured before release of UUO it was low (428 +/- 23 vs. 1,205 +/- 106 mosmol/kg in controls, P less than 0.001) which indicates that the decline in papillary osmolality is not a consequence of the increased IMPF seen after ureteral release, but rather precedes it. In fact, the decline in papillary osmolality may contribute to the increase in IMPF after release of UUO and to the decreased reabsorption of fluid along the descending limb of the loop of Henle.

Animals↗
PubMed1978

Adenylate cyclase of human parathyroid gland.

Experiments were performed on a particulate fraction from human parathyroid glands. A high activity of adenylate cyclase was detected which was linear with time and protein concentration. The enzyme had an optimum pH in the range of 7-8 and a Km for ATP of 0.44 X 10(-3) M. Ca++ had a profound inhibitory effect; a concentration of 0.5 mM Ca++ reduced enzyme activity by 60%. Maximal enzyme activity was obtained with 5 mM Mg++; higher concentrations of this cation also inhibited enzyme activity. The effect of Mn++ was similar to that of Mg++. Enzyme activity was stimulated by NaF, catecholamines, glucagon, and calcitonin. The effect of catecholamines seems to be mediated through beta-adrenergic receptors.

Adenoma↗
PubMed1977

T-cell deficiency in immune complex glomerulonephritis.

Mice chronically infected with the virus of lymphocytic choriomeningitis (LCM) develop immune complex glomerulonephritis. Others have shown that adoptive immunization of these mice by the i.p. injection of syngeneic immune spleen cells terminates the chronic viral carrier state. The present studies were designed to define the effector cell from the immune spleen responsible for adoptive immunization and to determine the effect of this procedure upon the immune complex nephritis which occurs in LCM carrier mice. The results indicate that the effector cell in adoptive immunization is a T-cell that functions directly as a killer cell when transferred to LCM carrier mice. Sixteen of nineteen adoptively immunized mice examined had less immune complex material deposited in their glomeruli than control unmanipulated litter mates. These data demonstrate that this animal model of immune complex glomerulonephritis is immunodeficient with respect to LCM virus-specific killer T-cells. Transfer of this cell population to the LCM carrier mouse diminishes the animal's viremia and improves its immune complex nephritis. In view of these observations, it is suggested that the rationale for the use of immunosuppressive therapy in spontaneously occurring glomerulonephritis should be carefully reconsidered.

Animals↗
PubMed1977

Effects of insulin, ADH, and cyclic AMP on sodium transport in the toad bladder.

These studies further define the mechanisms by which insulin stimulates Na transport in the toad bladder. Serosal but not mucosal addition of insulin, 100-1,000 mU/ml, stimulated short-circuit current (SCC) by 25-50%. The initial rise in SCC occurred at 5 min and the peak response at 15-25 min. Doses of insulin greater than 250 mU/ml increased SCC values for up to 3 h. Actinomycin D did not block the early rise in SCC produced by insulin, but it blocked the delayed effects. Insulin increased SCC in substrate-depleted bladders, although the increase in SCC was less (P less than 0.01) than in nonsubstrate-depleted bladders. Pyruvate addition to substrate-depleted bladders restored to normal the rise in SCC observed after insulin. Simultaneous addition of ADH and insulin led to an increase in SCC that was greater than the sum of the responses observed when each hormone was added independently. Synergistic effects on SCC were also obtained with cyclic AMP and insulin. Insulin did not increase cyclic AMP levels in toad bladder epithelial cells. It is suggested that insulin stimulates active Na transport by two mechanisms: 1) a rapid phase, which may involve unmasking of pump sites within the membrane, and 2) a delayed effect which seems to require protein synthesis. The synergism of which seems to require protein synthesis. The synergism of insulin with ADH or cyclic AMP may reflect a facilitative effect of insulin on ADH or cyclic AMP-sensitive pump sites or, alternatively, the uncovering of latent pump sites that then may be available to stimulation by ADH or cyclic AMP.

Animals↗
PubMed1977

Effects of ionophore A23187 on base-line and vasopressin-stimulated sodium transport in the toad bladder.

The cation specific ionophore A23187 (Io) is a useful tool for studying the role of intracellular Ca++ (Ca++)i in physiologic processes. The present studies explore the role of (Ca++)i on Na transport in the toad bladder. Scraped bladder cells exposed to 1 muM Io for 60 min took up 100% more 45Ca than control cells. Io, 1 muM, added to the serosal side of bladders incubated in standard Ringers containing 2.5 mM Ca++ inhibited short circuit current (SCC) values by a mean of 30% at 60 min and 50% at 90 min. Io did not inhibit SCC significantly in bladders incubated in Ringers containing 0.2 mM Ca++. These data indicate that the effects of Io on SCC depend on the levels of external Ca++ and suggest that entry of Ca++ into cells mediates the inhibition of base-line SCC. PReincubation of the bladders with either lanthanum chloride or pentobarbital prevented the increased 45Ca uptake produced by ionophore as well as theinhibition of SCC caused by the antibiotic. Vasopressin, antidiuretic hormone (ADH). 10 MU/ml, increased peak SCC by 247% in bladders preincubated for 1 h in Ringers with 2.5 mM Ca++ and 1 muM Io and by 318% in control bladders (P less than 0.01). Bladders exposed to 1 muM Io in Ringers with 0.2 mM Ca++ had an increase in SCC after ADH comparable to that observed in controls. Since the effects of ADH on SCC are mediated by cyclic AMP, we tested the effects of Io on cAMP production by scraped toad bladder cells. ADH increased cAMP from 8 to 30 pmol/mg protein in controls but it did not increase cAMP over base-line values in the presence of Io when the Ringers contained 2.5 mM Ca++. Io did not inhibit cAMP production in response to ADH when the Ca++ in the Ringers was 0.2 mM. The results indicate that Io inhibits baseline and ADH stimulated SCC by increasing (Ca++)i or Ca++ bound to the cell membrane. It is suggested that: ()( (Ca++)i or membrane-bound Ca++ plays a key role in base-line and ADH stimulated Na transport in the toad bladder; (2) inhibition of ADH stimulated SCC may be due inpart to decreased cAMP generation in response to ADH when (Ca++)i or membrane-bound Ca++ levels are increased.

Animals↗
PubMed1977

Effects of acute bilateral ureteral obstruction on deep nephron and terminal collecting duct function in the young rat.

The effects of acute bilateral ureteral obstruction (BUO) of 18-h duration on deep nephron and collecting duct function were studied by micropuncture in 11 weanling rats. After release of BUO glomerular filtration rate was reduced (178+/-15 vs. 1,343+/-119 mul/min per g kidney weight in shams), while urine flow was increased averaging 17.5+/-1.3 vs. 6.8+/-0.72 mul/min per g kidney weight in controls. There was a marked increase in the absolute and fractional excretion of Na. Single nephron glomerular filtration rate of deep nephrons was reduced in the BUO group, mean 19.4+/-3.5 vs. 77.0+/-7.7 nl/min per g kidney weight in shams. Single nephron glomerular filtration rate of superficial nephrons fell to the same extent after relief of BUO. Mean tubular fluid to plasma inulin ratio of fluid from Henle's loop was 2.46+/-0.20 after relief of BUO vs. 8.23+/-0.85 in shams. This suggested a reduction in the reabsorption of Na and water before the bend of the loop of Henle, most likely in both the proximal tubule and descending limb. Fluid osmolality was depressed due to a decline in both Na and nonelectrolyte solute content. After release of BUO the percentage of filtered water remaining in the collecting duct (CD) at the base of the papilla was greater than in controls (13.3+/-2.0 and 1.72+/-0.01%, respectively) but fell significantly by the tip of the papilla to 7.92+/-1.12 vs. 1.17+/-0.02% in controls. These results indicate that water was reabsorbed along the terminal CD after relief of ureteral obstruction. In fact, a greater fraction was reabsorbed in this segment after release of BUO (5.37+/-1.58%) than after sham operation (0.55+/-0.15%). Similar changes were seen in Na excretion. Thus alterations in deep nephron function appear to contribute to the natriuresis and diuresis which follow release of BUO while terminal CD function in this model appears intact.

Animals↗
PubMed1977

Degradation of parathyroid hormone and fragment production by the isolated perfused dog kidney. The effect of glomerular filtration rate and perfusate CA++ concentrations.

The renal degradation of intact bovine parathyroid hormone (b-PTH 1-84) was studied with the isolated perfused dog kidney. Disappearance of b-PTH 1-84 from the perfusate occurred concomitantly with the appearance of smaller molecular weight forms of immunoreactive parathyroid hormone (PTH). These smaller molecular weight PTH fragments included both carboxyl and amino terminal regions of the PTH peptide. Perfusate from kidneys with lower glomerular filtration rates (GFR) contained b-PTH 1-84 for longer periods of time than kidneys with higher GFRs, and perfusate from kidneys with lower GFRs demonstrated greater accumulation of carboxyl terminal PTH fragments. Perfusate containing high Ca++ concentrations retarded, and perfusate with low Ca++ concentrations accelerated the rate of degradation of b-PTH 1-84 by the kidney. These studies, therefore document the production of PTH fragments during the course of intact hormone degradation by the kidney. They also demonstrate renal clearance of the PTH fragments produced and define the effects of glomerular filtration rate and calcium concentrations on degradation of intact hormone and the clearance of PTH fragments.

Animals↗
PubMed1976

Effect of imidazole on renal gluconeogenesis.

The metabolic effects of imidazole were tested in rat renal cortex. Imidazole enhanced the activity of renal cortical phosphodiesterase in vitro. Imidazole inhibited glucose production in a dose-dependent fashion from a variety of substrates in the gluconeogenic pathway proximal to the triose phsophates. The stimulation in renal gluconeogenesis resulting from isoproterenol and parathyroid hormone was inhibited by imidazole. These changes correlated with an inhibition of the augmented levels of renal cortical cyclic AMP levels produced by these hormones. These studies indicate that imidazole is an effective activator of phosphodiesterase in intact renal cells and lend further support to the suggestion that the stimulation of renal gluconeogenesis produced by isoproterenol and parathyroid hormone is mediated by a release of cyclic AMP.

3',5'-Cyclic-AMP Phosphodiesterases↗