The behaviour of mammalian striated muscle in the presence of 2: 4‐dinitrophenol

Barnes, J. M.; Duff, Janet I.; Threlfall, C. J.

doi:10.1113/jphysiol.1955.sp005429

Cited by 27 publications

(12 citation statements)

References 26 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Production of contracture by other chlorophenols also suggests that these compounds are inhibitors of oxidative phosphorylation which would accord with their ability to stimulate oxygen uptake (see Table II). In the present experiments, contracture was preceded by slight potentiation of the twitch response; an effect which was not reported by Barnes et al (1955) for 2:4-dinitrophenol. Unfortunately, no explanation can be given for the potentiation of the twitch response produced by phenol, p-and m-monochlorophenols, and by 2: 6-dichlorophenol.…”

Section: Chlorination Of Phenol Produces a Series Ofsupporting

confidence: 48%

“…As shown by several authors (Weeks and Chenoweth, 1952;Judah and Magee, 1954;Barnes, Duff, and Threlfall, 1955), 2: 4-dinitrophenol sends the isolated rat diaphragm into contracture, this being accompanied by profound falls in the contents of creatine phosphate and adenosine triphosphate in the muscle. This production of contracture may be attributable to the ability of 2: 4-dinitrophenol to inhibit oxidative phosphorylation.…”

Section: Chlorination Of Phenol Produces a Series Ofmentioning

confidence: 99%

See 1 more Smart Citation

The Biological Action of Chlorophenols

Farquharson¹,

Gage²,

Northover

1958

British Journal of Pharmacology and Chemotherapy

View full text Add to dashboard Cite

The biological action of a series of chlorinated phenols has been investigated. With increasing chlorination there is an increase in toxicity in which the convulsant action of phenol is replaced by the signs characteristic of poisoning by dinitrophenol; the higher chlorinated phenols produce a contracture of the isolated rat phrenic nerve diaphragm and a stimulation of in vitro oxygen uptake of rat brain homogenate. These actions of the chlorinated phenols have been correlated with their dissociation constants; it is suggested that the higher chlorinated phenols interfere with oxidative phospborylation, and that this property may be attributed to the chlorophenate ion. The convulsant action of the lower chlorinated phenols is probably associated with the undissociated molecule.Chlorination of phenol produces a series of Employing eleven chlorophenols as well as nineteen compounds comprising mono-, di-, tri-, phenol itself, a systematic study has been made of and tetrachloro-isomers, and one pentachloro-the quantitative changes in toxicity occurring with form. All are crystalline solids at room tempera-progressive chlorination of phenol. Median lethal ture with the exception of orthochlorophenol doses have been taken as the basis for comparison which is a liquid. The lower compounds in the and have been determined under strictly controlled series are employed medically for their powerful conditions. An attempt has been made to correlate antiseptic properties which, in many cases, are these quantitative changes in toxicity with changes greater than those of phenol itself (von Oettingen, in the qualitative nature of the effects, and also 1949). Tetra-and penta-chlorophenols are impor-with the action on oxidative processes studied in tant wood preservatives, while the latter is also vitro. In turn, these changes have been considered used as a herbicide, fungicide, insecticide, and in conjunction with the dissociation constants of molluscicide. These uses of the higher chloro-the phenols. phenols have been reviewed by Truhaut, Vitte and The effect of the progressive chlorination of Boussemart (1952).phenol upon the isolated rat diaphragm has alsoOn account of the differences in test animals and been examined. injection techniques employed by authors, including the fact that only seven chlorophenols appear METHODS AND MATERIALS to have been studied, it is difficult to trace the way in which chlorination affects the toxicity of phenol carried out on male albino rats, weighing 125 to (Bechold and Ehrlich, 1906;Binet, 1896; Deich-175 g., which had been fasted for 24 hr. Experiments mann, 1943; Kehoe, Deichmann-Gruebler, and on rats which had received food prior to dosing Kitzmiller, 1939). The general effect of chlorina-showed a considerably lower toxicity. tion is to increase the toxicity while reducing Median lethal doses were determined by injecting the convulsant activity characteristic of phenol. the chlorophenols intraperitoneally in 10 ml. olivePentachlorophenol is non-convulsant and is oil/kg. body weight. Usin...

show abstract

Section: Chlorination Of Phenol Produces a Series Ofsupporting

confidence: 48%

Section: Chlorination Of Phenol Produces a Series Ofmentioning

confidence: 99%

The Biological Action of Chlorophenols

Farquharson¹,

Gage²,

Northover

1958

British Journal of Pharmacology and Chemotherapy

View full text Add to dashboard Cite

show abstract

“…This reduction depends on the long-lasting experimental procedure, according to Barnes, Duff & Threlfall (1955), who found that ATP concentration in rat diaphragms (kept in Tyrode solution at 370 C) falls, after 2 hr incubation, to mm 1.42/g of fresh tissue. The effect of DNP on choline acetyltransferase.…”

Section: Resultsmentioning

confidence: 99%

The Effect of 2,4‐dinitrophenol on Neuromuscular Transmission

Beani¹,

Bianchi²,

Ledda³

1966

British Journal of Pharmacology and Chemotherapy

View full text Add to dashboard Cite

In 1957 Kraatz and Trautwein carried out a detailed electrophysiological investigation to clarify the role of oxidative phosphorylation in the neuromuscular transmission of the frog. These authors demonstrated that 2,4-dinitrophenol (DNP) decreases end-plate potential (e.p.p.) height and increases miniature end-plate potential (m.e.p.p.) frequency, leaving their amplitude unaffected. Both effects were reversed by hyperpolarization of the motor nerve endings, suggesting that DNP affects the electrosecretory coupling and the spontaneous neurosecretion through reduction of transmembrane potential in nerve terminals. The prejunctional effect of DNP did not seem to depend on the exhaustion of transmitter stores because the effect was rapid in onset and the m.e.p.p.s maintained their amplitude, although their frequency greatly increased.However, the metabolic damage to the nerve (Abood, Koketsu & Noda, 1961) could, perhaps, not only impair the transmembrane ionic equilibrium, but also reduce the acetylcholine available for release, especially during prolonged nerve stimulation when the transmitter requirement and its synthesis rate increase considerably (MacIntosh, 1963). In view of this hypothesis, the effect of DNP on the mammalian neuromuscular junction has been re-examined, comparing the electrophysiological findings with the changes in acetylcholine release and stores in the presence of the drug.A preliminary account of some of these results has already been published (Beani, Bianchi & Ledda, 1963). METHODSThe experiments were performed in vitro using phrenic nerve-diaphragms obtained from guineapigs of either sex, weighing between 300-350 g, or from adult male (Wistar strain) albino rats, weighing between 200-250 g.Guinea-pig diaphragm. The left and right hemi-diaphragms of the same animal were set up in two separate baths each containing 4 ml. oxygenated Tyrode solution of the following composition: NaCl 137 mM; CaCl2 1.8 mm ; NaHPO4 0.3 mM; MgCl2 0.1 mM; NaHCO3 11.9 mM; glucose 11 mM. One hemi-diaphragm was treated with DNP, the other was kept as a control. Contractions were recorded on smoked paper with an isotonic lever; amplification 1:7, load 2 g. The stimulating rectangular pulses were of 0.1 msec duration for the indirect stimulation and 2 msec for the direct stimulation, which was performed with platinum electrodes applied to the costal margin of the muscle. The effect of DNP on the release of acetylcholine and on total tissue acetylcholine of Dyflos-pretreated preparations, at rest and indirectly stimulated at various frequencies, was examined L

show abstract

“…The phrenic nerve-diaphragm preparation of the rat can be used for studying the effects of uncoupling agents in vitro on contractions of the striated muscle of the diaphragm evoked by either stimulation of the phrenic nerve or direct stimulation of the muscle (Barnes, Duff and Threlfall, 1955). DNP (0.0465 ~tmol/ml) caused a decrease in contractions, those produced by phrenic nerve stimulation disappearing first followed by the gradual onset of a characteristic contracture.…”

Section: Io Imentioning

confidence: 99%