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PubMed1975

Respiratory effects of H+ and dinitrophenol injections into the brain stem subarachnoid space of fetal lambs.

Mock cerebrospinal fluid (pH 5.37-8.38) or 2,4-dinitrophenol (DNP) (0.15-1.5 mg) was injected into the subarachnoid space of the ventral brain stem of exteriorized fetal sheep. Changes in pH on the ventral surface of the medulla did not stimulate respiratory efforts or induce significant cardiovascular changes. The respiratory response to DNP injections ranged from no response to prolonged rhythmic ventilation that was independent of the peripheral chemoreceptors or the control arterial pH and blood gas tensions. This inconsistency suggests an effector site somewhat removed from the immediate surface of the medulla. The heart rate and blood pressure were not affected. It is concluded that increased H+ concentration in the extracellular fluid of the fetal ventral medulla does not initiate respiration, and any respiratory response to metabolic inhibitors applied to this area therefore is not attributable to a secondary change in surface pH.

Animals↗

PubMed1979

Role of peripheral tissue receptors in stimulation of ventilation by 2,4-dinitrophenol.

Previous workers have demonstrated that hindlimb receptors can mediate some portion of the increase in VE elicited by 2,4-dinitrophenol (DNP). Liang and Hood have recently demonstrated that these hindlimb receptors communicate with the respiratory center via afferent pathways of the lumbar spinal cord. Accordingly, to determine the quantitative contribution of these hindlimb receptors to increases in VE elicited by DNP (4 mg/kg), we compared two groups of animals with respect to ventilatory, metabolic, and thermal responses elicited by this drug. Group I animals underwent complete transection of the spinal cord at the first lumbar level, whereas the spinal cord in Group II animals remained intact. Our results indicate that Group I and Group II animals did not differ with respect to increases in VE, VO2, and rectal temperature elicited by DNP. These results suggest that hindlimb receptors do not play an obligatory role in mediating increases in VE elicited by DNP. Therefore, these observations raise the possibility that multiple afferent pathways may exist for stimulation of VE by DNP.

Animals↗

PubMed1975

Inhibition of thyroxine binding to adenohypophysial proteins in vitro by 2,4-dinitrophenol administered in vivo.

Male and female rats were given oestradiol benzoate (1 mg as a microcrystal aqueous suspension i.m. twice a week), 0.0033% 2.4-dinitrophenol (DNP) in their food (about 1 mg/rat/day), or 0.1% DNP in their food (about 30 mg/rat/day), or both oestradiol and DNP. The smaller DNP dose mildly stimulated food consumption and did not affect body weight. The larger dose strongly inhibited food consumption in the first two weeks of the experiment; consumption then returned to the control level, but body weight fell markedly at the same time. After 3 weeks' administration of both the small and the large dose of DNP, adrenal weight in the males was raised and the weight of the gonads was unchanged. The large DNP dose severely reduced the weight of the seminal vesicles and the uteri. It also inhibited the accumulation of radioiodine in the thyroid of both males and females. Isolated administration of the oestrogen raised adrenal weight in the males and ovarian and uterine weight in the females; it reduced the weight of the testes and seminal vesicles. These reactions were not affected by DNP. A pronounced oestradiol-induced increase in the weight of the adenohypophyses was accompanied by raised thyroxine binding to the adenohypophysial proteins in vitro. DNP inhibited the growth reaction of the adenohypophysis to the oestrogen only slightly and non-significantly, but significantly inhibited the thyroxine binding reaction to the adenohypophysial proteins in vitro. By itself, DNP had no effect on adenohypophysial weight, but reduced thyroxine binding to the adenohypophysial proteins in vitro, especially in males. The effect of DNP was similar to that of thyroxine observed in earlier experiments; nothing is known of its mechanism.

Adrenal Glands↗

PubMed1977

[Effect of maintaining the grassfrog sartorius muscle in a 0.002 M solution of alpha-dinitrophenol on its sensitivity to a 0.004 M solution of that substance].

A study was made of the effect of a preliminary maintenance of m. sartorius of Rana temporaria in 0.002 M alpha-dinitrophenol (alpha-DNP) on the resistance of muscles to 0.004 M concentration of this substance. The incubation of muscles in 0.002 M alpha-DNP for 10--20 min results in a statistically significant increase in their resistance to 0.004 alpha-DNP (24.8--30.7%). The highest increase in resistance was observed after a 20 minutes' maintenance of muscles. Therefore on studying the effect of 0.002 M alpha-DNP on the resistance of muscles to the injurious concentrations of chloral hydrate (0.08 M), ethanol (3.48 M), or 36 degrees, the muscles were maintained in the inhibitor for 20 minutes. In the case of a 20 minutes' maintenance of muscles in 0.002 M alpha-DNP, their resistance to chloral hydrate increased by 24.8%, whereas that to ethanol or heating decreased by 23.3 and 37.8--64.6%, respectively.

Animals↗

PubMed1979

Evidence for new factors in the coordinate regulation of energy metabolism in Escherichia coli. Effects of hypoxia, chloramphenicol succinate, and 2,4-dinitrophenol on glucose utilization, glycogen synthesis, adenylate energy charge, and hexose phosphates during the first two periods of nitrogen starvation.

We studied the effects of decreased aeration, chloramphenicol succinate, and 2,4-dinitrophenol on the cellular rates of glycogen synthesis and glucose utilization and on the cellular concentrations of adenine nucleotides, glucose 6-phosphate, fructose 1,6-diphosphate, and phosphoenolpyruvate during the first two periods of nitrogen starvation of Escherichia coli W4597(K). A quantitative relationship between the changes in the rates and the accompanying changes in the hexose phosphates is demonstrated. However, the relationship for glycogen synthesis is different in different sets of metabolic conditions. We suggest that this difference reflects a change in the steady state level of a previously unknown effector of ADP-glucose synthetase (glucose 1-phosphate adenylyltransferase, EC 2.7.7.27) the rate-limiting enzyme of bacterial glycogen synthesis. We show that the properties of the hypothetical in vivo effector are consistent with the inhibitory effects of ppGpp (guanosine 3'-diphosphate 5'-diphosphate) and pppGpp (guanosine 3'-diphosphate 5'-triphosphate) on this enzyme in vitro. In addition, tetracycline, an inhibitor of the synthesis of these nucleotides, apparently prevents the change in the quantitative relationship. The relationship between glucose utilization and the hexose phosphates is altered at the transition to Period II of nitrogen starvation. We propose that this change reflects the alteration of the cellular steady state level of an unknown effector of the glucose phosphotransferase system. In contrast to the ATP-hexose phosphate system of shared regulatory effects, the specific effects of the unknown effectors allow the rates of glucose utilization and glycogen synthesis to be altered independently of each other and independently of changes in the rate of glycolysis. This independence allows a greater latitude of response for the individual pathways in more severe metabolic stress or in accommodating the metabolic changes necessary for long term survival.

Adenine Nucleotides↗

PubMed1979

[Effect of cycloheximide, 2,4-dinitrophenol and papaverine on ribosomal RNA synthesis in Ehrlich ascitic carcinoma cells].

The influence of 2,4-dinitrophenol (DNP), papaverine and cycloheximide on RNA synthesis in Ehrlich ascites tumour cells has been investigated. All above mentioned agents inhibit selectively synthesis of high-molecular rRNA precursor, when the cell population density is 3.10(7)--5.10(7) per 1 ml of suspension. When the density of cells decreases as far as 1.10(6) cells per 1 ml. the rRNA synthesis loses the sensitivity to all these agents. The effects of both cycloheximide on the protein synthesis and DNP on ATP level do not depend on the cell population density in suspension. It is suggested that either with a decrease of cell population density the protein synthesis and ATP level cease playing the role of a rate-limiting factor in the rRNA synthesis, or the influence of agents studied is realized by means of their interaction with other cell system.

Adenosine Triphosphate↗

PubMed1979

Effect of different factors modifying the activity of some enzyme systems of the endoplasmic reticulum on the sensitivity of cell organelles against the damaging action of chemical agents. II. Studies with chlorpromazine, 2,4-dinitrophenol, phenobarbital and DDT.

Further investigations on the effect of different stress factors on the stability of intracellular membranes were carried out. Large granule fractions derived from livers of sleep-deprived and dehydrated rats and subjected to preincubation at 37 degrees and pH 5 were shown to release latent acid phosphatase with a delayed rate indicating an increased lysosomal stability towards acid media conditioning. Lysosomes of such animals, however, were found to be more sensitive to mechanical treatments (homogenization procedure in this case) than that of controls, a conclusion made on the basis of enhanced "free" and nonsedimentable phosphatase activities in liver homogenates. The stress factors which previously were included in the group of modifiers of the activity of the endoplasmic reticulum-located enzymes caused some changes in the action of certain chemicals on membranes. Earlier such changes were elicited for carbon tetrachloride and only on low-temperature-conditioned rats for chlorpromazine. The present results show that stress factors studied result in deviations (different in extent and in direction) from the usual effects of chlorpromazine, 2,4-dinitrophenol, phenobarbital and DDT on liver lysosomes and peroxisomes.

Acid Phosphatase↗

PubMed1975

On the mechanism of the glycogenolytic effect of dinitrophenol. Activity of phosphofructokinase in perfused hearts.

To explain the mechanism of DNP action the contents of ATP, ADP, AMP and G-6-P were determined in perfused rat hearts in a period of time in which the rate of the glycogenolysis was increased. The levels of these metabolytes in the extract were consistent with an increase of the phosphofructokinase activity. On the other hand, the finding of higher activity of phosphyrylase beta kinase in DNP-poisoned animals could be explained as due to the low content of G-6-P in the perfused hearts subjected to the action of the drug.

Adenine Nucleotides↗

PubMed1975