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T V Zenser

Publications and source records attributed to T V Zenser.

At least 145 records · Page 8Linked to original sources
PubMed1978

Impaired inner medullary production of prostaglandin E2 in the kidney of the myxedematous rat.

Renal cAMP concentration and renal prostaglandin (PG) E2 and PGF2alpha production were determined in control rats and rats with surgically induced myxedema. Slices from the kidneys of each group were incubated in vitro. cAMP concentration of inner medullary slices from the kidneys of myxedematous rats was decreased in comparison to slices from control rats. There was no difference between the two groups when slices from outer medulla and cortex were compared for cAMP level. In myxedema, there was decreased inner medullary production of PGE2, but not PGF2alpha. The difference in PGE2 production between myxedema and control rat kidneys was not corrected by addition of either arachidonic acid (170 micronM) or phospholipase A2 (5 microgram/ml). Arachidonic acid, however, increased inner medullary cAMP concentration in myxedema kidneys to a value not measurably different from control. Thus, there appears to be a decreased PGE2 production in the renal inner medulla of rats with myxedema. In view of the fact that PGE2 has previously been shown to increase inner medullary cAMP content, the reduced inner medullary content of cAMP would appear to be attributable to reduced PGE2 production.

Animals↗
PubMed1978

DDAVP (1-desamino-8-D-arginine-vasopressin) treatment of central diabetes insipidus--mechanism of prolonged antidiuresis.

DDAVP, 1-desamino-8-D-arginine-vasopressin, is a synthetic analog of arginine vasopressin which produces prolonged antidiuresis after intranasal administration to patients with complete central diabetes insipidus. We have studied the mechanism of the prolonged antidiuretic effect by specific radioimmunossay of DDAVP in plasma of patients and by in vitro studies on the adenylate cyclase-cylic AMP system of the rat outer renal medulla. When DDAVP was administredd to patients, all responded, but the duration of response among patients varied from 5-21 h. The peak level of DDAVP in plasma was achieved up to 4 h after administration indicating a slow absorption from the nasal mucosa. The disappearance time of DDAVP from plasma correlated significantly with the duration of antidiuresis, P less than 0.001. On a molar basis DDAVP was 3-fold greater than AVP in its stimulation of outer medullary adenylate cyclase activity and 10-fold greater than AVP in its stimulation of cyclic AMP content. The prolonged antidiuresis of intranasally administered DDAVP is due to slow absorption, presistence in plasma, and enchanced effect on the kidney.

Adenylyl Cyclases↗
PubMed1978

Kidney metabolism of acetaminophen and phenacetin.

The metabolism of acetaminophen and phenacetin by rabbit kidney slices was investigated. Phenacetin, like aspirin, inhibited [131I] Hippuran accumulation by the organic acid transport system. Phenacetin exhibited a dose-dependent inhibition with a K1 of 0.5 mM; acetaminophen at concentrations as high as 1 mM did not alter organic acid transport. [3H] acetaminophen slice: media ratios of approximately 1 or less suggested that acetaminophen entered cortex and outer and inner medullary slices by diffusion rather than active transport. Approximately 95% of the acetaminophen within the slices readily diffused out into the media. The chromatographic patterns of this material were similar to that of the incubation media. The acetaminophen remaining within the slices was acid-precipitable and not extractable with organic solvents. This covalent binding of acetaminophen was inhibited by glutathione. More acetaminophen was bound in the renal medullar than cortex. These data suggest that the renal metabolism of acetaminophen observed in this in vitro study may be related to the nephritis observed in analgesic abuse.

Acetaminophen↗
PubMed1977

Effect of oxygen and solute on PGE and PGF production by rat kidney slices.

Increasing oxygen from 5% to 95% resulted in an increases production of both PGE's and PGF's. The release of prostaglandins from slices of rat kidney cortex and outer and inner medulla was measured. Prostaglandin production was observed predominantly in the inner medulla, was close to the lower limit of detection in the outer medulla, and was undetectable in the cortex. Increasing oxygen concentration resulted in a threefold increase in inner medullary prostaglandin production. Synthesis at 95% O2 was less at 2100 mOsm than at 300 mOsm, while synthesis at 5% O2 was not affected by high solute concentration. The implications of these results with respect to kidney function are discussed.

Animals↗
PubMed1977

Prostaglandin E2 production by renal inner medullary tissue slices: effect of metabolic inhibitors.

Increasing oxygen from 5 to 95% has previously been shown to increase prostaglandin (PG) production in renal inner medullary slices. The possible role of oxidative phosphorylation in this process was investigated. The oxidative phosphorylation inhibitors, dinitrophenol (DNP), oligomycin, and cyanide were evaluted for their effects on PGE2 production and ATP levels. None of the inhibitors affected PGE2 synthesis, although they lowered ATP levels at the concentrations tested. In contrast, incubation of inner medullary tissue slices with 0% oxygen resulted in decreases both in PGE2 and ATP levels. This suggests that the effect of oxygen on prostaglandin synthesis may be due to substrate limiting effects rather than an effect on oxidative phosphorylation. When 22 mM 2-deoxyglucose was added to the incubation medium or when glucose was omitted, PGE2 levels increased. Sodium fluoride, presumably acting as a glycolytic inhibitor, increased PGE2 levels, with a maximal effect at 10 mM. ATP levels were 37% of control values with 20 mM NaF. This indicates that glucose may inhibit prostaglandin synthesis. These results indicate that oxygen (substrate) availability can limit inner medullary PGE2 production. In view of the low pO2 in the inner medulla, especially during antidiuresis, oxygen can potentially regulate prostaglandin production in this tissue.

Adenosine Triphosphate↗
PubMed1977

Effects of prostaglandins on rat renal adenylate cyclase-cyclic AMP systems.

The effects of prostaglandin (PG) E1, E2, A1, F1alpha, F2alpha or D2 on the rat renal cortical, outer medullary and inner medullary adenylate cyclase-cyclic AMP systems were examined. While high concentrations (8X10-4M) of each prostaglandin stimulated adenylate cyclase activity in each area of the kidney, PGE1 was the only prostaglandin to stimulate at 10-7M. PGA's were the only prostaglandins tested besides PGE's which stimulated adenylate cyclase at less than 10-4M. This effect of PGA's was limited to the outer medulla. PGD2 was the least stimulatory. Observations with renal slices yielded qualitatively similar results. The PGE's were the most potent in each area with PGA's only stimulatory in the outer medulla. O2 deprivation (5% O2) lowered the slice cyclic AMP content in each area of the kidney. In the cortex and outer medulla, prostaglandin mediated increases in cyclic AMP content were either lower or absent at 5% O2 compared to 95% O2. However, in the inner medulla PGE stimulation was observed only at 5% O2 and not 95% O2. No other prostaglandins were found to increase inner medullary cyclic AMP content at 95% or 5% O2. These results illustrate that the adenylate cyclase-cyclic AMP system responds uniquely to prostaglandins in each area of the kidney. Consideration of these results along with correlative observations suggests that inner medullary produced PGE's may act as local modulators of inner medullary adenylate cyclase.

Adenylyl Cyclases↗
PubMed1977

Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses.

Crude mediators from stimulated rabbit peritoneal leukocytes (LEM) engender numerous physiologic alterations in rats, which are similar to those observed during infection. One hour after the intraperitoneal injection of crude LEM, plasma insulin and glucagon concentrations are elevated; at 2 h the hormonal alterations are manifested by a 30% increase in hepatic cyclic adenosine 3',5'-monophosphate (cAMP), glycogen depression, and uptake of 14C-labeled nonmetabolizable amino acid analogues (AA). Plasma hormone concentrations reach maximum levels by 5 h and decline by 24 h. The hepatic concentrations of AA parallel the insulin and glucagon responses and correlate with the inverse of insulin/glucagon molar ratio. In spite of mobilization of hepatic glycogen evident at 5 h, plasma glucose concentrations were transiently depressed. Plasma insulin, glucagon, and hepatic AA concentrations were dose dependent. Plasma insulin and glucagon responses to crude LEM may explain increases in hepatic cAMP, uptake of AA, and glycogenolysis as well as hypoglycemia. These data partially characterize the role of crude LEM, provide an explanation for the stimuli-inducing hyperglucagonemia and hyperinsulinemia during infection. They implicate the endocrine pancreas as a factor regulating the host's metabolic response to infection.

Amino Acids↗
PubMed1976

Spin-labeled stearates as probes for microenvironment of murine thymocyte adenylate cyclase-cyclic adenosine 3':5'-monophosphate system.

The interaction of various spin-labeled compounds with the murine thymocyte adenylate cyclase-cyclic AMP system was investigated. Electron paramagnetic resonance spectra from spin-labeled compounds were used to calculate the order parameter, S, and indicated that the thymocyte plasma membrane is a relatively rigid structure. Increasing concentrations of spin-labeled stearates, but not their corresponding methyl esters, resulted in increased membrane fluidity, partial lysis, and concomitant complete inhibition of cholera toxin-mediated increases in cyclic AMP content. Upon subsequent isolation of plasma membranes from these cells, cholera toxin-stimulated adenylate cyclase activity was also completely inhibited. Direct addition of spin-labeled stearates, but not spin-labeled methyl stearates, to thymocyte homogenates caused a dramatic reduction of basal, cholera toxin-, isoproterenol-, NaF-, and prostaglandin E1-stimulated adenylate cyclase activity. Inhibition was complete within the first minute of addition to homogenates and required approximately 0.2 mM spin-labeled stearate I(12,3) for half-maximal inhibition. This inhibition occurred in the presence or absence of an ATP-regenerating system and was not readily reversible. Furthermore, since the membrane cyclic phosphodiesterase activity was not altered by spin-labeled stearates, their inhibition was attributed to a direct action of stearate spin labels on adenylate cyclase. Neither stearate, methyl stearate, spin-labeled methyl stearates nor 2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempo) altered cell viability or enzyme activities at the concentrations studied. Spin-labeled stearates seemed to intercalate into different areas of the plasma membrane than their corresponding methyl esters. Furthermore, the action of spin-labeled stearates appeared to be on the exterior of the plasma membrane rather than the interior. These results illustrate the presence of multilipid domains and the importance of selected lipids and lipid-protein interactions in the adenylate cyclase-cyclic AMP system. Thymocyte adenylate cyclase is described in terms of a current model for membrane proteins.

Adenylyl Cyclases↗
PubMed1976

Properties of cholera toxin- and NaF-stimulated adenylate cyclase from mouse thymocytes.

Kinetic parameters of mouse thymocyte adenylate cyclase activity were determined. NaF and cholera toxin stimulated adenylate cyclase. Stimulation by either agent did not change the pH or Mg2+ optima relative to control (unstimulated cyclase). The Km value for ATP of adenylate cyclase stimulated by NaF was significantly reduced from control. By contrast, cholera toxin treatment did not change the Km relative to control. Adenylate cyclase, when stimulated by NaF, had an optimum for Mn2+ alone, or Mn2+ in combination with Mg2+, at least twice that of control. In contrast, cyclase activity prepared from cells treated with cholera toxin remained unchanged with regard to these divalent cations when compared to control. Addition of NaF to adenylate cyclase prepared from cells treated with cholera toxin resulted in a significant reduction (30%) in activity suggesting that both NaF and cholera toxin were acting on the same cyclase. NaF inhibition of cholera toxin-stimulated activity was shown to be a direct interaction of fluoride on the stimulated cyclase enzyme. This inhibition appeared to be immediate and independent on pH, Mg2+ or ATP concentrations. Although NaF inhibition was lost when Mn2+ was present in the reaction mixture, the activity expressed by addition of NaF to cyclase prepared from cholera toxin-treated cells was much less than by addition of NaF to control. As observed with cholera toxin stimulation alone, activity expressed by the inhibited enzyme (cholera toxin treated + NaF) exhibited a Km for ATP and an optimum for Mn2+ alone or in combination with Mg2+ similar to control.

Adenylyl Cyclases↗
PubMed1976

Mechanism of inhibition of organic acid transport in rabbit renal cortex by cyclic AMP.

The mechanism by which isoproterenol and cyclic AMP inhibit organic acid transport was examined. Accumulation of 131I-Hippuran (S/M) was used as an index of organic acid transport. Propranolol, an antagonist of isoproterenol's beta-adrenergic response, not only inhibited accumulation of Hippuran but, when combined with isoproterenol, caused further inhibition. PTH elicited larger increases than isoproterenol in cortical-slice cyclic AMP content but did not inhibit accumulation of Hippuran. This lack of correlation between a positive effect on the adenylate-cyclase-cyclic AMP system and inhibition of transport was also seen when other agents were tested. Cyclic GMP, which has been postulated to work in opposition to cyclic AMP, was as potent as cyclic AMP in decreasing S/M. The decreasing of S/M by adenine and uric acid could not be related to any known effect of these agents on tissue cyclic AMP content. Similarly, although 0.1 mM theophylline significantly decreased S/M, cortical cyclic-AMP content was not increased until a 100-fold greater concentration of theophylline was employed. The data suggest that the inhibitory effect of these agents was attributable to their molecular configurations, which interact directly with the organic acid transport system rather than indirectly via the adenylate-cyclase-cyclic AMP system.

Adenine↗
PubMed1976

Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis.

Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.

Animals↗