Injection Of ATP Research Articles

The turnover of phosphorus compounds in crab muscle fibres.

1. The exchange of 32P injected into single crab muscle fibres as either orthophosphate or ATP has been studied. The results have been analysed in terms of a simple kinetic model. 2. The exchange of 32P between ATP and arginine phosphate is considerably faster than that between ATP and orthophosphate during rest and during contraction in caffeine. 3. The rate constants obtained at rest after the injection of either orthophosphate or ATP labelled with 32P were of the same order. They were also of the same order as those which have been obtained previously for squid axons. 4. The exchange during caffeine contraction of 32P unjected as orthophosphate gave rate constants which were consistent with an increased rate of splitting of ATP and with the rate constants needed to account for the observed net formation of orthophosphate. The results obtained after the injection of 32P-labelled ATP during caffeine contraction were less clear cut.

Coronary responses to dilating substances and competitive inhibition by theophylline in the isolated perfused guinea pig heart.

Coronary dilation induced by infusion of adenosine, adenine nucleotides, dipyridamole, and papaverine was quantitated in the spontaneously beating isolated perfused guinea pig heart. Theophylline antagonized the effects of all the substances tested. The inhibition proved to be reversible and of a competititve type. Single injections of ADP and ATP induced flow increases which were more rapid in onset and of greater magnitude than those due to equimolar amounts of adenosine. Lowering the perfusate temperature prolonged coronary responses to ADP and ATP more than those to adenosine. Papaverine produced greater maximal dilation than adenosine. Theophylline inhibited papaverine-induced dilation less effectively than dilating responses to adenosine and other compounds. In the potassium arrested heart, the dilation caused by compound D 600 and papaverine was sensitive to the perfusate calcium concentration but that due to adenosine was unaffected. Dipyridamole, which was equipotent to adenosine in the non-arrested hear, became less potent than adenosine in the arrested heart. The results favour the view that all of the substances tested induce coronary dilation per se and that their effects are not mediated by adenosine. The dilator response to papaverine is assumed to be the result of two effects, one of which is inhibited by theophylline, the other by high extracellular calcium.

TIEREXPERIMENTELLE UND KLINISCHE UNTERSUCHUNG ZUR WIRKUNG VON COENZYM A AUF DIE FETTELIMINATION BEI DER FETTLEBER

Based upon the experimental results in KK and ddY/S-mice, it has become clear that a combination of Coenzyme A and Adenosine triphosphate exercises a favorable influence on treatment of the fatty liver. Forty one patients have been complaining of general fatigue more than one year. Their bodyweight exceeded slightly the standard in their own age. Physical examination revealed slight enlargement of the liver. Laboratory findings: hyperbetalipoproteinemia, hypercholesterinemia, hyperbetaglobulinemia, pathologic BSP-retention, slight elevation of cholin esterase and transaminaseactivity. Glucose toleranse test with 50g resulted in latent or manifest diabetic curve. Immunoreactive insuline (IRl) was also estimated. Liver biopsy: fatty liver. The treatment with a combination of 8mg CoA and 30mg 219 ATP daily in the form of intramuscular injection was introduced into the medical treatment when needle biopsy of the liver revealed steatosis hepatis histologically in these patients. After therapeutic duration of 6 months, laboratory findings as well as histological features of the biopsied liver specimens were improved. Therefore, it can be said that simultaneous i.m. injection of CoA and ATP brings a favorable effect not only on the laboratory findings but also on the histological changes of the fatty liver with diabetic change.

Changes in unit activity of medullary respiratory neurons after intravenous injection of ATP.

Changes in unit activity of medullary respiratory neurons after intravenous injection of ATP.

Simultaneous ATP-AET-serotonin protection of spermatogonia from mutations induced by 300 R x-rays in the mouse.

SummaryProtection of spermatogonia from dominant lethal mutations induced by acute whole-body X-irradiation (300 R) was studied in C57BL mice given a simultaneous injection of AET, ATP and serotonin. Evidence was obtained that simultaneous administration of these radioprotectors significantly reduced dominant lethality. Expected and observed rates of post-implantation loss were found to be of the same order of magnitude.

Mobility and transport of magnesium in squid giant axons.

1. The Mg content of axons obtained from Loligo forbesi averaged 6.4 +/- 0.8 m-mole/kg axoplasm.2. A small patch of radioactive (28)Mg injected into an axon broadened considerably. A similar patch of (45)Ca showed hardly any broadening. The self-diffusion coefficient of Mg in axoplasm is about 2 x 10(-6) cm(2)/sec which is at least twenty times greater than that of Ca.3. Under the influence of an applied electric field Mg migrated towards the cathode. Its mobility was about half of that of Mg in free solution. This suggests that the concentration of ionized Mg in squid axoplasm is between 2 and 3 m-mole/kg axoplasm. The mobility of Mg was not changed by poisoning the axon fully.4. Mg influx and Mg efflux were roughly the same and equal to about 1 p-mole/cm(2) sec. Mg efflux was reduced by poisoning with cyanide and by replacement of external Na by choline. Removal of external K or Ca had little effect and removal of external Mg tended to increase the efflux.5. The dependence of Mg efflux on Na seems not to be secondary to changes in Ca because it persists in the absence of external Ca and in axons pre-injected with EGTA. The form of the dependence on Na ions approximates to a simple rectangular hyperbola.6. Replacement of external Na by Li or choline increased Mg influx. Mg influx was unaffected by cyanide.7. Mg efflux was reduced to an average of 15% by poisoning with cyanide or DNP. The efflux could be recovered by injection of ATP. Inhibition persisted in axons pre-injected with EGTA, showing that it is not secondary to a rise in Ca(i).8. During nervous activity there is an extra entry of Mg. For axons immersed in sea water this extra Mg entry per impulse is roughly the same as the extra Ca entry per impulse.

Calcium dependence of ciliary activity in the oviduct of the salamander Necturus.

1. Ciliary activity in the oviduct of the mud puppy Necturus maculosus was monitored by a photometric technique in normal, decalcified, and Triton X-extracted preparations to investigate the regulatory role of calcium ions.2. The frequency of ciliary beating in the isolated tissue ranged from 0 to 12 beats/sec. The frequency in any one group of cells underwent large cyclical variations with periods of 2 min or more.3. Frequency of beating reached a maximum and remained at a plateau upon addition of 1 mM caffeine. Beating temporarily ceased upon removal of the caffeine.4. Ionophoretic injection of calcium ions into an active cell bathed in Ringer solution produced an increased rate of beating. In cells rendered quiescent by prior decalcification with EGTA, injected calcium rapidly restored ciliary activity.5. Epithelia extracted in Triton X-100 were inactive until reactivated by addition of ATP and magnesium ions. The frequency of beating increased between 0.1 and 4.0 mM ATP in 1 mM magnesium, and between 0.2 and 2.5 mM magnesium in 1 mM ATP.6. The frequency of beating in the ATP-reactivated, Triton-extracted tissue was independent of the calcium ion concentration.7. Cells inactivated by decalcification were reactivated by injection of ATP or by extracellular ATP levels as low as 3 x 10(-8)M.8. It is concluded that the frequency of beating depends directly on the concentration of the available energy source, presumably ATP, and that an indirect dependence of beating frequency on calcium concentration in the living tissue results from rate-limiting effects of intracellular calcium on metabolic steps in pathways leading to ATP synthesis.

ATP vascular reactivity after chronic adrenalectomy

Adrenalectomy has been shown to decrease the reactivity of the isolated rat hind quarters to single injections of ATP. It is postulated that this reactivity change might be the result of a change in membrane calcium following adrenalectomy.

Non‐cholinergic transmission by post‐ganglionic motor neurones in the mammalian bladder

1. In mucosa-free preparations of the detrusor muscle electrical stimulation with 0.1 msec pulses has been utilized to reveal the non-cholinergic nature of most, if not all, of the post-ganglionic motor neurones in the guinea-pig bladder.2. The twitches elicited by 0.1 msec pulses were abolished by tetrodotoxin, but were not reduced by dimethyltubocurarine or by hexamethonium. Hexamethonium was nevertheless present in all the experiments in order to restrict acetylcholine action to ;muscarinic' receptors in the muscle fibres.3. There was little or no diminution in the twitches after prolonged exposure to atropine, 10(-8)-10(-5) g/ml., although the twitch-matching dose of acetylcholine was raised 1000-2500 times. Hence, there was no anomalous refractoriness to atropine in these ;muscarinic' receptors.4. Despite massive atropinization, the recruitment of unoccupied transmitter-receptors by means of extra pulses remained unaffected.5. Eserine failed to potentiate the atropine-resistant twitches.6. The twitches were not depressed by morphine.7. Noradrenaline produced relaxation and twitch reduction. The twitches persisted after alpha + beta adrenoceptor blockade with phentolamine + pronethalol and were unaffected by the monoamine oxidase and catecholamine-O-methyl transferase inhibitors, tranylcypromine and pyrogallol.8. Rapid contractions were elicited by 5-HT and by histamine but the twitches remained unaltered after antagonism of 5-HT by methysergide and of histamine by mepyramine.9. The twitches could be mimicked by injections of ATP, but after desensitization of the preparation to ATP the response to electrical stimulation remained unaltered.10. Prostaglandins E(2) and F(2alpha), only in large doses, produced delayed, sluggish contractions which persisted after the wash; these contractions were quite different from the responses to electrical stimulation, which were immediate, sharp and brief.11. The non-cholinergic nature of the post-ganglionic motor neurones was confirmed in the bladder of two other species, the cat and the rabbit.

Permeability of a cell membrane junction. Dependence on energy metabolism.

The ion permeability of the membrane junctions between Chironomus salivary gland cells is strongly depressed by treatments that are generally known to inhibit energy metabolism. These treatments include prolonged cooling at 6 degrees -8 degrees C, and exposure to dinitrophenol, cyanide, oligomycin, and N-ethylmaleimide. Intracellular injection of ATP appears to prevent depression of junctional permeability by dinitrophenol or to reverse it. Ouabain, azide, p-chloromercuriphenylsulfonic acid, reserpine, and acetazolamide fail to depress junctional permeability. Thus the ion permeability of the junctional membranes appears to depend on energy provided by oxidative phosphorylation. Possible energy-linked processes for maintaining junctional permeability are discussed, including processes involving transport of permeability-modifying species such as Ca(++).

Effects of ethionine on thyroid function.

Three hr after injection of dl-ethionine in the rat, thyroid ATP concentration was significantly (p<.01) lowered, the mean value being 0.38 μmole/g, while the control value was 0.66 μmole/g. At this time interval, both T/S and T/M radioiodide concentration ratios were also lowered by ethionine injection. Concurrent injection of methionine, adenine or ATP prevented both glandular ATP depletion and reduction of T/S and T/M induced by ethionine alone. Injection of ATP or adenine increased glandular ATP above control values, but did not affect iodide transport. Although ethionine greatly impaired thyroid organification of administered Iiodide, it did not prevent injected TSH from stimulating organic binding, enhancing thyroid iodine depletion, or raising the serum PBI concentration. By contrast, ethionine given together with TSH prevented the increment in glandular NADP induced by TSH alone. The results suggest that reduction of thyroid ATP concentration impairs iodide transport. The stimulatory action of TSH...

A Course of Medical Treatment of Sudden Deafness and Its Effect

On the basis of biochemical and clinical examinations, the new therapeutic measure of sudden deafness has been presented according to an assumption that a large proportion of sudden deafness was due to impairment of the inner ear caused by abnormal blood circulation.From January through October in 1963, 34 cases were treated with special importance on the following points: (1) improvement of the inner ear blood circulation, (2) activation of oxidative phosphorylation (by means of an intravenous injection of ATP in large amount) and (3) activation of general metabolism.The results of the above series were compared with thoses of 59 cases treated in the preceding 10 years by the combined use of vasodilators and vitamin B complexes.(1) The new treatment produced a marked effect in 61% of fresh cases and in 71% of sub-fresh cases, while the old treatment only 37% and 35% in each category. Neither method was effective in cases older than 14 days.(2) In cases of total hearing loss, the old treatment produced effect in less than 10% of the cases, while the new treatment raised the efficacy to 40%. However no one patient made a perfect recovery.(3) The presence of vestibular symptom produced no significant difference between the effect of both methods.Relationship between the results of audiometrical examinations and the effect of the new treatment:(1) Observing their hearing curve and prognosis, it was found that the prognosis of cases with slope fall at low frequency and flat curve was relatively good, whereas those with steep fall at high frequency had the worst prognosis.(2) In regard to hearing recovery process, cases making an even recovery over total frequency were observed most often. Generally however, the recovery in high frequency was not good.(3) There were 2 cases of spontaneous recovery among 34 cases. Both of them made a remarkable recovery in low frequency.The relationship between the results of clinical examinations and the effect of the new treatment:(1) In cases where inner ear hemorrhage was suspected the new method gave negligible benefit.(2) The new treatment was relatively effective in cases of hypo-tension. A mildly positive virological test was found in one of 8 fresh cases.

Stimulation of secretion of insulin by adenosine-triphosphate.

IN previous papers1–4 we showed that different metabolites, both in vivo and in vitro, produce insulin secretion which we measured by the method of the epididymal fat of the rat. In view of some of these results we decided to ascertain whether the intravenous injection of ATP was a stimulant to insulin secretion; although we are aware that the point of view actually held is that the metabolic processes affected by this nucleotide are intracellular.

EFFECTS OF VARIOUS VASODILATOR DRUGS ON CEREBRAL CIRCULATION

1. The changes in cerebral hemodynamics and metabolism were measured by N20 method after the administration of various vasodilator drugs. 2. A decrease in CBF and an increase in CVR were observed by the administration of caffein, theophylline ethylendiamine and oxyethyl-theophylline. No changes were observed in both CBF and CVR by diethyl-amino-ethyl-theophylline and Parmanil. 3. ATP caused no effect on CBF, but a slight fall of CVR. CMRO2 increased significantly by intravenous injection of ATP together with 40% glucose solution. A decrease in CBF and an increase in CVR were observed by Lacarnol, but these changes were not statistically significant. No significant changes were seen in CBF and CVR after the intravenous administration of Kallikrein. 4. Priscol and nicotinid acie produced no changes in CBF, CVR and CMRO2. An insignificant increase in CBF and CMRO2 was seen by the administration of Vasculat, acetylcholine and amyl-nitrite. Papaverine hydrochloride is the only agent among several vasodilators used at present by which a certain increase in CBF occurs.

On the Effect of Gastric Hormone “Productin” to the Parietal Cells

In order to find the factor which dominates the function of the parietal cell, the authors performed the experiments of administering sesame oil orally into the starved rats (exp. 1), of administering sesame oil after the injection of Atp. (exp. 2), of injecting subcutaneously an extract of the gastric mucosa of the pig (exp. 3) and of injecting Atp. then Hist. (exp. 4).After administration of sesame oil, production of the secretory substance becomes remarkable in the parietal cell, big granules and the wide light part appear. On the other hand, the apex of the cell opens into the lumen and the cell shows the function of discharging the secretory substance. Both discharge and production reach the maximum 60min. later. After this the secretory substance is discharged completely and produced again continuously. These functional movements, especially the productive functions, are very interesting because they are quite coincidental with the movements of the productinvacuoles in the surface cells of the gastric mucosa.However if Atp. is injected before sesame oil administration, the functional images of the parietal cells, both production and discharge, are less active and end early. The productin-vacuoles of the surface cells in this case decrease a little and soon increase again. According to these observations it is considered that the function of the parietal cells is dominated greatly by productin. This will be demonstrated more certainly by following two results, that the parietal cell shows the similar remarkable movements to the ones following the administration of sesame oil after the injection of a gastric extract (exp. 3) and that it shows a very marked production and discharge after the injection of Atp. and Hist. (exp. 4).By addition of the results obtained here, to the ones which have been obtained previously by FUJIE, the authors reached the following conclusions:1. The greatest factor dominating the function of both the peptic and the parietal cells in the gastric gland is productin, secreted from the surface cells of the gastric mucous membrane into the blood.2. The automatic nerves give greater influences to the productinsecretion in the surface cells rather than to the secretion in the gastric gland cells.