scholarly journals Effect of halothane on metabolism of 5-hydroxytryptamine by rat lungs perfused in situ

1983 ◽  
Vol 210 (1) ◽  
pp. 157-166 ◽  
Author(s):  
C A Watkins ◽  
S A Wartell ◽  
D E Rannels

The effect of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on the uptake of 14C-labelled 5-hydroxytryptamine (5-HT) and its metabolism to 5-hydroxyindol-3-ylacetic acid (5-HIAA) was investigated in rat lungs perfused in situ. The rate of accumulation of 14C-labelled 5-HIAA in the tissue, monitored as an index of 5-HT metabolism, was linear with time, displayed saturation kinetics and remained stable for at least 180 min of perfusion. Exposure of the lungs to halothane (4%) for 60 min reversibly reduced production of 5-HIAA through an increase in the apparent Km for metabolism of the amine from 1.45 to 3.52 microM (P less than 0.001); the anaesthetic had no effect on the Vmax. of the process. The magnitude of the inhibition increased with time of exposure to the anaesthetic. Halothane exposure did not alter the distribution of [3H]sorbitol or [14C]5-HT, pulmonary vascular resistance, levels of ATP or the kinetics of amino acid transport in the tissue. Inhibition of protein synthesis by cycloheximide did not mimic the effect of the anaesthetic. These observations, together with those made in lungs exposed to inhibitors of 5-HT uptake and metabolism, were consistent with a halothane-mediated inhibition of 5-HT uptake, which did not appear to involve non-specific changes in membrane permeability.

1985 ◽  
Vol 249 (5) ◽  
pp. E506-E513 ◽  
Author(s):  
D. E. Rannels ◽  
A. E. Pegg ◽  
R. S. Clark ◽  
J. L. Addison

The kinetics of [14C]paraquat (N,N-di[14C]methyl-4,4'-bipyridylium) uptake from the pulmonary circulation were investigated in rat lungs perfused in situ. During the 1st h of exposure to the herbicide paraquat entered the lungs primarily by diffusion; no evidence was obtained from concentrative uptake, saturation kinetics (1-3,500 microM paraquat), or inhibition by the amines methyl-glyoxal bis(guanylhydrazone) or spermidine, both of which were expected to compete for paraquat transport sites. In contrast, after 60 min of exposure, uptake rates increased two- to three-fold, and paraquat was accumulated to an apparent intracellular concentration greater than that in the perfusate. The latter phase of paraquat uptake was saturable and was inhibited by methylglyoxal bis(guanylhydrazone); it did not appear to reflect a progressive paraquat-induced alteration in cellular permeability but rather predominance of a rapid, carrier-mediated uptake pathway.


1975 ◽  
Vol 19 (1) ◽  
pp. 127-139
Author(s):  
M. Frank ◽  
S.B. Horowitz

Ultra-low temperature techniques (microdissection and autoradiography) were used to study the nucleocytoplasmic distribution and transport of alpha-aminoisobutyric acid (AIB) in an amino acid-accumulating cell. In amphibiam oocytes incubated in AIB, the nuclear concentration of this non-metabolizable amino acid exceeds the cytoplasmic concentration by 45%, remaining constant both over time and variation in substrate concentration. The kinetics of uptake suggest that this nucleo-cytoplasmic asymmetry arises from solubility differences between the 2 compartments, and that the nuclear envelope plays a negligible role in amino acid transport. A solute exclusion model is offered to explain the nucleocytoplasmic asymmetry.


1979 ◽  
Vol 51 (3) ◽  
pp. S252-S252 ◽  
Author(s):  
D. B. Rannels ◽  
C. A. Watkins ◽  
J. F. Biebuyck

1989 ◽  
Vol 257 (3) ◽  
pp. E379-E384
Author(s):  
D. C. Martin ◽  
A. M. Carr ◽  
R. R. Livingston ◽  
C. A. Watkins

The effects of ketamine and fentanyl on serotonin (5-hydroxytryptamine; 5-HT) metabolism, angiotensin-converting enzyme (ACE), and protein synthesis (PS) were investigated in an isolated lung model. Rat lungs were perfused in situ with a blood-free physiological salt solution. The pulmonary vasculature was exposed to ketamine (0.005-2.1 mM) or fentanyl (1.8-4.5 microM) for up to 2 h. After 1 h, accumulation of 5-[14C]hydroxyindoleacetic acid (5-HIAA) by the lung was monitored as an index of 5-HT metabolism. ACE activity was estimated from hydrolysis of [3H]benzoylphenylalanyl-alanyl-proline, a synthetic substrate for the enzyme. [3H]phenylalanine was added to the perfusate after 1 h, and its incorporation into acid-precipitable lung protein was measured over the subsequent hour. Ketamine inhibited 5-HT uptake in a concentration-related manner. The inhibition was characterized as competitive and reversible. Fentanyl had no effect on lung 5-HIAA accumulation. Neither drug altered ACE activity or protein synthesis over the concentration ranges tested. The results indicate an action by ketamine that inhibits the 5-HT membrane-transport process. The different effects observed by ketamine and fentanyl on this process could contribute to the diverse pharmacological properties of these two drugs.


1975 ◽  
Vol 53 (10) ◽  
pp. 1442-1448 ◽  
Author(s):  
Bernard Descamps ◽  
Wendell Forst

The pyrolyosis of CF3OOCF3 (BTMP) was studied in the gas phase from 5 to 100 Torr BTMP pressure and between 197 and 244 °C in a clean nickel reactor by the static method. CF3O radicals, due to the initial split[Formula: see text] were scavenged by SO3F radicals produced in situ by the thermal decomposition of their dimer S2O6F2. Under these conditions, CF3OOSO2F is the only product of BTMP pyrolysis, as shown by gas chromatographic analysis. Thus the BTMP pyrolysis becomes fully inhibited and the rate of accumulation of CF3OOSO2F is a measure of k1. The rate constant k1 turns out to be pressure-insensitive under the experimental conditions, from which it is inferred that k1 is actually k1∞, the limiting high-pressure unimolecular rate constant for reaction 1. Its temperature dependence yields the result[Formula: see text]This result is compared with other values of the O—O bond dissociation energy in BTMP. The experimental expression for k1 ∞ is used to construct the pressure falloff of k1 following the procedure of Forst. The calculation confirms that falloff begins only below 10 Torr.


Author(s):  
J. Drucker ◽  
R. Sharma ◽  
J. Kouvetakis ◽  
K.H.J. Weiss

Patterning of metals is a key element in the fabrication of integrated microelectronics. For circuit repair and engineering changes constructive lithography, writing techniques, based on electron, ion or photon beam-induced decomposition of precursor molecule and its deposition on top of a structure have gained wide acceptance Recently, scanning probe techniques have been used for line drawing and wire growth of W on a silicon substrate for quantum effect devices. The kinetics of electron beam induced W deposition from WF6 gas has been studied by adsorbing the gas on SiO2 surface and measuring the growth in a TEM for various exposure times. Our environmental cell allows us to control not only electron exposure time but also the gas pressure flow and the temperature. We have studied the growth kinetics of Au Chemical vapor deposition (CVD), in situ, at different temperatures with/without the electron beam on highly clean Si surfaces in an environmental cell fitted inside a TEM column.


Author(s):  
R-R. Lee

Partially-stabilized ZrO2 (PSZ) ceramics have considerable potential for advanced structural applications because of their high strength and toughness. These properties derive from small tetragonal ZrO2 (t-ZrO2) precipitates in a cubic (c) ZrO2 matrix, which transform martensitically to monoclinic (m) symmetry under applied stresses. The kinetics of the martensitic transformation is believed to be nucleation controlled and the nucleation is always stress induced. In situ observation of the martensitic transformation using transmission electron microscopy provides considerable information about the nucleation and growth aspects of the transformation.


Author(s):  
M. Park ◽  
S.J. Krause ◽  
S.R. Wilson

Cu alloying in Al interconnection lines on semiconductor chips improves their resistance to electromigration and hillock growth. Excess Cu in Al can result in the formation of Cu-rich Al2Cu (θ) precipitates. These precipitates can significantly increase corrosion susceptibility due to the galvanic action between the θ-phase and the adjacent Cu-depleted matrix. The size and distribution of the θ-phase are also closely related to the film susceptibility to electromigration voiding. Thus, an important issue is the precipitation phenomena which occur during thermal device processing steps. In bulk alloys, it was found that the θ precipitates can grow via the grain boundary “collector plate mechanism” at rates far greater than allowed by volume diffusion. In a thin film, however, one might expect that the growth rate of a θ precipitate might be altered by interfacial diffusion. In this work, we report on the growth (lengthening) kinetics of the θ-phase in Al-Cu thin films as examined by in-situ isothermal aging in transmission electron microscopy (TEM).


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