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At least 19 recordsLinked to original sources
PubMedDate not supplied

Binding of organic compounds to rat liver and lung.

The binding of various radioisotopically labeled organic compounds to rat liver and lung was investigated in vitro. Pieces of rat lung and slices of rat liver were incubated at 37 degrees C under a nitrogen atmosphere in a modified Krebs-Ringer phosphate solution (pH 7.4) CONTAININg the compound to be studied. Of the neutral compounds investigated, digitoxin, digoxin and dexamethasone were highly bound to both liver and lung tissue, whereas the degree of binding of amitrole, erythritol, and ouabain was 20% or less. The weak acids which were bound to the greatest extent in both liver and lung were phenobarbital, pentobarbital, and diphenylhydantoin. Barbital was poorly bound, and there was no evidence for the binding of 5,5-dimethyloxazolidine-2,4-dione or p-aminohippuric acid in either tissue. Binding of the cardiac glycosides and the barbiturates directly paralleled their lipid solubilities. The degree of binding of neutral compounds and weak acids to lung and liver tissue did not vary greatly with concentration, even though broad concentration ranges were studied. This was also true of the weak base morphine. On the other hand, the binding to liver and lung of the organic bases nicotine, pilocarpine, d-amphetamine, lidocaine, erythromycin, and chloroquine, did vary with concentration. The quaternary ammonium compound decamethonium was bound only to liver, and this binding also varied with concentration. Two additional quaternary ammonium compounds, tetraethylammonium and N1-methylnicotinamide, were not significantly bound to either tissue. Comparisons on the basis of equal content of solids revealed that the binding of diverse organic compounds in liver is greater than or equal to that in lung.

Amitrole↗
PubMed1978

Effect of tetramethylammonium ions on conformational changes of DNA in the premelting temperature range.

The reversible conformational change of DNAs and polydeoxyribonucleotides occurring before melting was followed by circular dichroism. deltatheta/deltaT, the rate of change of ellipticity theta with temperature, was used mainly as a measure of this premelting phenomenon. If sodium ions were replaced by tetramethylammonium ions deltatheta/deltaT decreased for poly (dA) poly (dT) and poly (dA.dT) poly (dT.dA), but increased for poly (dG.dC) poly (dC.dG). DNAs of different base composition showed no more premelting (deltatheta/deltaT approximately 0) even at low molarities of TMACl provided the Na/TMA ratio was very small. For all cases studied the theta values at 0 degrees C and at a given ionic strength were smaller in NaCl than in TMACl. When studying the series of ammonium ions from NH4+ to (C2H5)4N+, the deltatheta/deltaT values first decreased, going through zero with TMA+ ions, and then increased again. A tentative and qualitative explanation of our results can be given: (a) Hydration of the polymers increases in presence of TMA ions and their average stability decreases; locally, however, (AT) pairs are preferentially stabilized by TMA ions owing to a specific interaction at the level of O2 of thymine. (b) In order to explain the different behaviour of (AT) polymers and DNA, it is assumed that only the B structure is able to accommodate TMA ions in the small groove of the double stranded helix.

Chemical Phenomena↗
PubMed1977

Effects of strychnine on the potassium conductance of the frog node of Ranvier.

The nature of the block of potassium conductance by strychnine in frog node of Ranvier was investigated. The block is voltage-dependent and reaches a steady level with a relaxation time of 1 to several ms. Block is increased by depolarization or a reduction in [K+]O as well as by increasing strychnine concentration. A quaternary derivative of strychnine produces a similar block only when applied intracellularly. In general and in detail, strychnine block resembles that produced by intracellular application of the substituted tetraethylammonium compounds extensively studied by C.M. Armstrong (1969. J. Gen Physiol. 54:553-575. 1971. J. Gen. Physiol. 58:413-437). The kinetics, voltage dependence, and dependence on [K+]O of strychnine block are of the same form. It is concluded that tertiary strychnine must cross the axon membrane and block from the axoplasmic side in the same fashion as these quaternary amines.

Action Potentials↗
PubMedDate not supplied

Effects of citrinin on renal tubular transport functions in the rat.

The fungal toxin, citrinin, has been implicated as a nephrotoxin. Both in vitro and in vivo studies were undertaken to examine, in a controlled laboratory setting, the effects of citrinin on overall renal function as well as on specific renal transport processes. At a dose of 70 mg/kg citrinin caused an increase in urine production and a decrease in urine osmolality in the Sprague-Dawley rat. Maximal effects were observed at 4 days after a single dose, and animals surviving for that time period regained normal renal function by 5--8 days. Animals that failed to survive first entered a period of oliguria or anuria. Fischer 344 rats did not demonstrate an unusual sensitivity to citrinin. Renal slice transport of various organic compounds, e.g., paminohippurate (PAH) and tetraethylammonium (TEA), also was inhibited with maximal effects seen at day 4. In vitro effects of citrinin on fresh renal tissue were different, in part, from the effects seen with pretreatment. No alterations of renal cortical inorganic electrolytes were observed.

Animals↗
PubMed1977

Effect of sodium salicylate on renal elimination of a quaternary ammonium compound.

Administration of sodium salicylate inhibited elimination of the tetraethylammonium ion in rats. A two-compartment open model was used to describe plasma decline of tetraethylammonium bromide administered intravenously. The rate constant describing elimination from the central compartment was decreased by 25 and 40% in rats predosed with sodium salicylate at 30 and 50 mg/kg, respectively. Salicylate also enhanced the distribution of the tetraethylammonium ion to the peripheral compartment. Urinary excretion is the principal route of elimination for the tetraethylammonium ion, and studies of the effect of sodium salicylate on the uptake of the tetraethylammonium ion by rat renal cortical tissue indicated noncompetitive inhibition by salicylate.

Animals↗
PubMed1978

Analysis of frog neuromuscular function at hyperbaric pressures.

Nerve and muscle compound action potentials were measured in the frog sciatic nerve-gastrocnemius muscle preparation in a hyperbaric helium-air environment. Helium pressure to 69 ATA induced a reversible depression in muscle compound action potential amplitude without significantly affecting other parameters. Blockade other parameters. Blockade induced by tetraethylammonium while at pressure could be partially reversed by decompression. A desensitization-type of neuromuscular block produced at pressure after neostigmine infusion could also be partially reversed by decompression. These results suggest a possible involvement of the acetylcholine receptor complex in pressure-induced depression of synaptic transmission.

Acetylcholine↗
PubMed1979

In vivo direct effects of cholinergic agents on the inferior mesenteric and cardiac ganglia with relation to their receptors in the dog.

The relative contribution of nicotinic and muscarinic receptors to the cholinergic transmission of the inferior mesenteric ganglion was studied in spinal dogs by recording changes in perfusion pressure of the inferior mesenteric artery as an indicator of ganglionic function. Preganglionic stimulation elicited a frequency (2.5--320 Hz)-dependent rise in the perfusion pressure, which was inhibited by i.v. hexamethonium (C6) (10 mg/kg) or atropine (0.1 mg/kg) administered after C6. Acetylcholine (ACh) (0.1--1000 microgram) administered into the inferior mesenteric artery to reach the mesenteric ganglion induced a dose-dependent rise in perfusion pressure and this dose-response curve was shifted to the right by C6 or atropine. Bethanechol (1--1000 microgram) i.a. produced a dose-dependent rise in the pressure, which was abolished after i.v. atropine. Tetramethylammonium (1--300 microgram) i.a. elicited an increase in the pressure thought the effects were decreased at larger doses, and these effects were strongly inhibited by i.v. C6. ACh (5--100 microgram) administered into the right subclavian artery to reach the cardiac sympathetic ganglia caused a dose-dependent positive chronotropic effect, which was inhibited by i.a. C6 or atropine. The results suggest that the inferior mesenteric ganglion seems to differ from the cardiac ganglia in relative contribution of nicotinic and muscarinic receptors to the cholinergic transmission.

Acetylcholine↗
PubMed1979

Mechanism of blockage of amphotericin B channels in a lipid bilayer.

A number of organic compounds (non-electrolytes, tetraalkylammonia, etc.) with a molecular size of 6--8 angstrom decrease the conductance of ionic channels formed in the lipid bilayer by a polyene antibiotic amphotericin B. It is suggested that these compounds, upon entering the channel, block the passage of inorganic ions. The extent of conductance blockage by organic ions depends on the membrane potential and electrolyte concentration. In the presence of ionic blockers, for instance tetraethylammonium, amphotericin B-containing membranes assume some properties characteristic of excitable membranes, i.e. the current-voltage characteristic acquires the negative resistance region, and in response to a potential step activation followed by inactivation of conductance is observed. It is shown that the potential dependence of the blockage is due to interaction inside the channel of the blocker ion with penetrating ions, by a mechanism similar to that described by Armstrong ((1979) Q. Rev. Biophys. 7, 179--210) for blockage of squid axon potassium channels by ammonium derivatives.

Amphotericin B↗
PubMed1977

Depression of renal clearance of furosemide in man by azotemia.

The renal clearance of furosemide and tetraethylammonium (TEA) were compared in 10 patients with hypertensive nephropathy. BUN and creatinine ranges were 10 to 88 mg/dl and 0.9 to 3.8 mg/dl, respectively. Diuretics were discontinued 48 hr prior to the study, and 2 consecutive clearances (ml/min/1.73 m2BSA) of creatinine were performed. The patient then received a bolus followed by a constant infusion of furosemide-14C and tetraethylammonium-14C (analyzed by specific methodology for plasma and urine), both in subpharmacologic doses. After 40-min equilibration sequential 20-min clearance periods were obtained. Both the clearance of furosemide (range 17 to 133) and TEA (range 99 to 443) correlated negatively with BUN and serum creatinine and positively with creatinine and urea clearances. Thus, by using a constant-infusion technique we demonstrated that the renal clearance of furosemide is depressed by azotemia in man and that there was greater depression with furosemide than with TEA.

Adult↗