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Studies on streaming. I. Inhibition of protoplasmic streaming and cytokinesis of Chaos chaos by adenosine triphosphate and reversal by magnesium and calcium ions.

In Chaos chaos streaming, motility, and cytokinesis were inhibited nearly 100% for several hours by 2.5-5 mM sodium adenosine triphosphate (ATP)(1) added to culture fluid. All three effects were completely prevented by the addition of equimolar Mg(++) or Ca(++) ions but not Na(+) to the ATP/culture fluid solution. The effects of ATP were not reproduced by EDTA, EGTA, colchicine, or AMP. Sodium pyrophosphate produced about 50% inhibition at 5 mM. Studies with (14)C-ATP showed that 5 x 10(-5) to 5 x 10(-4) mmole of ATP was firmly associated with each milliliter of packed cells after an hour's incubation at 24 degrees C. Labeling studies also showed that prevention of the ATP effects by Mg(++) ions was not due to a decrease in the amount of ATP associated with the cells.

Adenine Nucleotides↗

Evidence for species-specific substrate-site-directed inactivation of rabbit adenylate kinase by N6-(6-iodoacetamido-n-hexyl)adenosine 5'-triphosphate.

Adenosine 5'-triphosphate (ATP) derivatives bearing iodoacetylamino-n-alkyl substituents [(CH2)nNHCOCH2I] on N6 were synthesized as potential ATP-site-directed irreversible inhibitors of adenylate kinases from rabbit, pig, and carp muscle. When n was 5 no enzyme was progressively inhibited (inactivated) by 1 mM inhibitor under the test conditions (6 h at 0 degrees); when n was 6 the rabbit enzyme was 76% inactivated by 0.79 mM inhibitor whereas the pig and carp enzymes were unaffected by 2.76 mM inhibitor; when n was 7, 1 mM inhibitor inactivated 14% of the rabbit enzyme and did not inactivate the pig and carp enzymes; when n was 8, all enzymes were inactivated 11-15% by 1 mM inhibitor. No inactivation occurred when the iodine of the hexamethylene analogue was replaced by hydrogen. The selective effect occured also in mixtures of the rabbit and pig enzymes and evidence could not be found that the hexamethylene analogue was activated by the rabbit enzyme or deactivated by the pig and carp preparations. The species-specific inactivation in concluded from various lines of evidence to be ATP-site-directed and is attributed to alkylation of an amino acid residue of the rabbit enzyme which in the pig and carp enzymes is absent, inaccessible, or less reactive. These and previous studies with several other enzymes provide evidence that substrate-site-directed agents capable of bonding covalently to an amino acid residue outside the substrate site can be designed to exert species-specific or tissue-specific irreversible inhibition of target enzymes.

Adenosine Triphosphate↗

Determination of susceptibility of Staphylococcus aureus to methicillin by luciferin-luciferase assay of bacterial adenosine triphosphate.

Susceptibility of 50 strains of Staphylococcus aureus to methicillin was determined by disc diffusion, minimum inhibitory concentration (MIC) test and luciferin-luciferase assay of bacterial adenosine triphosphate (ATP). ATP concentration time curves calculated on eight strains (four sensitive, four resistant) incubated at 30 degrees C indicated 2.5 h as the optimum time for determination of methicillin susceptibility. The ATP concentration and relative light unit (RLU) value of each test broth (antibiotic-containing), expressed as a percentage of its own control broth (antibiotic-free) indicated values of less than 30% for ATP and less than 40% for RLU to be indicative of methicillin sensitivity. Single time point ATP assays carried out on the 50 strains after 2.5 h at 30 degrees C correlated exactly with disc diffusion and MIC. Luciferin-luciferase assay of bacterial ATP appeared to be a reliable, rapid technique for determining the susceptibility of Staph. aureus to methicillin.

Adenosine Triphosphate↗

An adenosine triphosphate (ATP)-sensitive K+ channel of rat neocortical neurons is bi-gated by intracellular ATP and voltage: a novel channel gating mechanism?

To determine whether the adenosine triphosphate (ATP)-sensitive K+ (K-ATP) channels, which are suggested to be mainly regulated by intracellular ATP or other kinds of triphosphate nucleotides, are gated by membrane potentials (Vm), single K-ATP channel currents were studied on inside-out membrane patches of neurons acutely dissociated from Sprague-Dawley rat neocortex. The K-ATP channels recorded have a unitary conductance from 96.97 +/- 5.32 pS (n = 11) at potentials of approximately 10-60 mV to 98.31 +/- 3.26 pS (n = 11) at approximately -10 to -60 mV. Besides being inhibited by cytoplasmic ATP, channel kinetics was also affected by Vm. Open- and closed-time histograms were well fitted by 2 exponentials, suggesting that the channels have 2 open and closed states. Mean open time (tau om), open probability increased while mean closed time (tau cm) decreased with depolarization. The fitted equations of the relationships between Vm and those kinetic parameters may be described as: tau om = -159.26lnV + 403.64, Po = -0.01Vm2 + 0.08Vm + 0.87 and tau cm = 0.17Vm3-2.5Vm2 + 10.35Vm - 7.68, respectively. We suggest that the K-ATP channels be bi-gated by both intracellular ATP and membrane potentials. This property of the neuronal K-ATP channels may be related to their pathophysiological functions.

Adenosine Triphosphate↗

[Adenosine triphosphate in the peroperative management of hypertensive crises and heart rate disorders in the surgical treatment of pheochromocytoma].

OBJECTIVE: To assess the hypotensive and antiarrhythmic effect of adenosine triphosphate (ATP) and its impact on hypertensive crises and heart rhythm abnormalities resulting from surgery to remove pheochromocytoma. PATIENTS AND METHODS: A prospective study of 7 patients with pheocromocytoma who were scheduled for unilateral (4) or bilateral (3) suprarenalectomy prior to treatment with phenoxybenzamine and propranolol. The anesthetic procedure was the same for all patients, as was monitoring: ECG, digital pulse oximetry, capnography, direct recording of arterial pressure by a catheter in the left radial artery and a Swan-Ganz fiber optic catheter in the pulmonary artery to measure pulmonary pressures and mixed venous oxygen saturation. Minute volume was measured by thermodilution. Blood glucose levels and urine excreted through a catheter were recorded hourly during surgery. During surgery, when arterial pressure had risen 20% above baseline level, i.v. infusion of ATP 0.5 mg/kg/min was begun and adjusted up or down depending on patient response. Infusion was stopped when the suprarenal vein had been tied. Hemodynamic analysis was performed during 4 phases: 1) start of surgery; 2) during manipulation of the tumor; 3) after excision, and 4) after surgery. Hemodynamic and metabolic variables were recorded, as were ATP doses and requirements for vasopressors and antiarrhythmic drugs. RESULTS: We found the following changes between phase 1 and phase 2, coinciding with ATP infusion: systemic arterial pressure increased 22.2%, heart rate increased 28.04% (with no cardiac arrhythmia observed in any patient), pulmonary artery pressure rose 25.35%, pulmonary capillary pressure rose 22.17%, cardiac index rose 108% while systemic vascular resistance decreased 55.82% and pulmonary vascular resistance decreased 33.96%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

The effect of experimental gastric dilatation-volvulus on adenosine triphosphate content and conductance of the canine gastric and jejunal mucosa.

The objective of this study was to determine if experimental gastric dilatation volvulus (GDV) would decrease adenosine triphosphate (ATP) concentration and increase membrane conductance of the canine gastric and jejunal mucosa. Male dogs (n = 15) weighing between 20 and 30 kg were used. Dogs were randomly assigned to 1 of 3 equal groups: Group 1 was control, group 2 was GDV, and group 3 was ischemia. All dogs were anesthetized for 210 min. Group 1 had no manipulation. Group 2 had GDV experimentally induced for 120 min followed by decompression, derotation, and reperfusion for 90 min. Group 3 had GDV experimentally induced for 210 min. Gastric (fundus and pylorus) and jejunal tissue was taken at 0, 120, and 210 min from all of the dogs. Tissue was analyzed for ATP concentration, mucosal conductance, and microscopic changes. The ATP concentration in the fundus did not change significantly from baseline in group 2, but decreased significantly below baseline at 210 min in group 3. The ATP concentration in the jejunum decreased significantly below baseline in groups 2 and 3 at 120 min, remaining significantly decreased in group 3 but returning to baseline at 210 min in group 2. Mucosal conductance of the fundus did not change significantly in any dog. Mucosal conductance of the jejunum increased at 120 min in groups 2 and 3, and became significantly increased above baseline at 210 min. The jejunal mucosa showed more profound cellular changes than the gastric mucosa. The jejunum showed substantial decreases in ATP concentration with an increase in mucosal conductance, suggesting cell membrane dysfunction. Dogs sustaining a GDV are likely to have a change in the activity of mucosal cells in the jejunum, which may be important in the pathophysiology of GDV.

Adenosine Triphosphate↗

Effects of norepinephrine on the distribution of intestinal blood flow and tissue adenosine triphosphate content in endotoxic shock.

OBJECTIVE: To investigate, during endotoxic shock, the effect of a treatment of norepinephrine (NE) administration on the distribution of blood flow and adenosine triphosphate (ATP) content in the intestinal wall. DESIGN: Randomized controlled trial. SETTING: Animal laboratory. SUBJECTS: Domestic pigs. INTERVENTION: A total of 18 pigs were anesthetized with ketamine and pentobarbital, mechanically ventilated, hemodynamically monitored, and then challenged with a continuous infusion of Escherichia coli endotoxin (ET) (15 microg/kg) for 2 hrs. Three groups of six animals were studied; one served as time control, one group received ET and fluid resuscitation, and a third group received ET, fluid resuscitation, and a perfusion of NE to maintain constant mean arterial pressure (MAP). MEASUREMENTS AND MAIN RESULTS: Cardiac output, mesenteric arterial blood flow, MAP, pulmonary pressure, and portal pressure were measured. Intestinal mucosal intracellular pH (pHi) was determined with saline-filled balloon tonometers. Tissue blood flows to the intestinal mucosa and to the muscular layer were independently measured with fluorescent microspheres, using the arterial reference sample method. Measurements were performed before and 3 hrs after the start of the ET challenge. At the end of the experiments, muscularis and mucosal samples were quickly frozen for further enzymatic ATP measurements. ET administration with fluid resuscitation induced a distributive shock with increased mucosal blood flow and decreased muscularis blood flow, whereas pHi decreased and mucosal ATP content was significantly lower than in the control group. In the group receiving ET plus NE, MAP remained constant, mucosal blood flow did not increase, and mucosal ATP content was equal to the time control group. Meanwhile, mucosal acidosis was not prevented. CONCLUSIONS: Normodynamic endotoxic shock may induce an alteration in mucosal oxygenation, despite an increased tissue blood flow. A treatment of NE combined with fluid resuscitation has complex effects on tissue blood flow, ATP content, and pHi.

Adenosine Triphosphate↗

The effect of estrogen replacement therapy on platelet aggregation and adenosine triphosphate release in postmenopausal women.

OBJECTIVE: To evaluate the effect of hormone replacement therapy on platelet function in postmenopausal women. METHODS: In 51 postmenopausal women, platelet aggregation and adenosine triphosphate (ATP) release were studied before and after estrogen and progestogen treatment and compared with that in untreated patients. An incubation study evaluated platelet function after incubation with estrogen and progestogen. RESULTS: Significant decreases in adrenaline-induced platelet aggregation (P < .01) and ATP release (P < .02) were observed 3 months after initiation of estrogen replacement. Patients receiving replacement regimens consisting of estrogen opposed by progestogen or progestogen alone showed nonsignificant changes in platelet aggregation and release. The most pronounced decrease in platelet function in the incubation assay was detected after incubation with estrogen plus progestogen. Results were similar in the spontaneous- and surgical-menopause patients. CONCLUSION: Estrogen replacement therapy may inhibit the atherosclerotic process by suppressing platelet function.

Adenosine Triphosphate↗

The effect of the platelet count on the aggregation response and adenosine triphosphate release in an impedance lumi-aggregometer.

Platelet aggregation studies are usually performed in either electrical impedance or optical systems and the release reaction assessed by quantitating adenosine triphosphate (ATP) from luminesence produced by the firefly luciferin-luciferase system. In evaluating the results of such studies, attention is paid to a variety of parameters such as the slope of the aggregation response and the maximum aggregation expressed as percent light transmission in optical and as Ohms in electrical impedance systems. Although threshold platelet counts are frequently cited below which the performance of these studies is technically difficult, the influence of the platelet count within the normal range on the results of such studies has not been prospectively addressed. This study examines the relationship between the aggregation response, ATP release and the platelet count in a lumi-impedance system. It is clear that the platelet count influences the results in this system and requires consideration in the interpretation if an erroneous conclusion is to be avoided.

Adenosine Diphosphate↗

Oxygen deprivation and early myocardial contractile failure: a reassessment of the possible role of adenosine triphosphate.

The precise mechanism responsible for early contractile failure after the onset of myocardial anoxia or ischemia has attracted speculation and controversy. The simple and attractive hypothesis that adenosine triphosphate (ATP) deficiency is responsible for this failure has often been dismissed on the basis of claims that there is only a small reduction in cell ATP content at a time when contractile activity is severely reduced. The premise of this article is that the changes in cell ATP content and distribution that theoretically should occur after oxygen depletion may not have been adequately considered and that previous measurements of cell ATP content may not have been carried out at the correct time. Using an isolated rat heart preparation and high speed freeze-clamping techniques it has been possible to demonstrate that a substantial decrease in myocardial ATP and creatine phosphate content occurs after the onset of anoxia but before the onset of contractile failure. Thus, during the first 5 seconds of anoxia contractile activity remains constant whereas ATP decreases by 25 percent and creatine phosphate by 50 percent. Thereafter, contractile failure occurs and the rate of utilization of high energy phosphates declines with the cell content at a plateau or possibly increasing. These results are assessed in the light of the dynamic changes in energy metabolism occurring in early anoxia and suggest that ATP depletion in a specific cell compartment may be the primary trigger for early contractile failure.

Adenosine Triphosphate↗

The effect of adenosine triphosphate, magnesium chloride and phospholipids on crystal formation in the demineralized shell-repair membrane of the snail, Helix pomatia L. An in vitro study.

The effect of adenosine triphosphate (ATP), magnesium chloride (MgCl2) and phospholipids on the calcium-binding activity and crystal formation within the decalcified shell-repair membrane of the snail, Helix pomatia, was studied in vitro. The application of ATP produced a characteristic dual effect on calcification: (1) It strongly inhibited the formation of inorganic calcium carbonate (CaCO3) crystals. (2) It stimulated the development of organic crystalline bodies and induced deposition of amorphous calcium carbonate. The demineralized shell-repair membranes became white and rigid after incubation for 7 days in the medium containing 1.0 mM ATP. The inhibitory effect of Mg2+ on CaCO3 crystal formation was diminished by reduction of the concentration of MgCl2 in the incubation solution. Thus, after incubation for only 24h, 1.0 mM MgCl2 promoted the formation of birefringent CaCO3 crystals within the repair membranes. The principal effect of phospholipids on the demineralized shell-repair membrane was stimulatory, but after application of phospholipids to the medium, the formation of crystals proceeded slowly. The very large, composite crystals that were formed within the repair membranes showed strong birefringence. In all cases the development of the crystals and the organic crystalline bodies occurred in close vicinity to the amoebocytes. The role of ATP, MgCl2 and phospholipids in the recalcification of shell-repair membrane is discussed.

Adenosine Triphosphate↗

Oxygen-induced pulmonary vasodilation is mediated by adenosine triphosphate in newborn lambs.

In the fetal lamb, oxygen-induced pulmonary vasodilation is attenuated by the combined use of purinergic receptor P1 and P2y antagonists, which block the effect of adenosine and adenosine triphosphate (ATP), respectively, and by N(omega)-nitro-L-arginine [an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis]. In the newborn lamb, oxygen-induced pulmonary vasodilation is not blocked by N(omega)-nitro-L-arginine. We investigated the role of ATP and adenosine in oxygen-induced pulmonary vasodilation in eight newborn lambs with pulmonary hypertension induced by the thromboxane mimic, U46619. The hemodynamic effects of hyperoxia, ATP, adenosine, sodium nitroprusside (SNP), and acetylcholine (ACh) were compared before and after purinergic receptor blockade with Cibacron blue (CB, a P2y-receptor antagonist) and 8-phenyltheophylline (8PT, a P1-receptor antagonist) individually, together, and on a separate day, after infusion of N(omega)-nitro-L-arginine. During pulmonary hypertension, combined pretreatment with 8PT and CB attenuated the decrease in pulmonary arterial pressure caused by hyperoxia (11.3 vs. 35.2%), ATP (10.6 vs. 32.2%), and adenosine (1.9 vs. 33.7%) without change in the effect of ACh or SNP (p < 0.05). N(omega)-Nitro-L-arginine attenuated the pulmonary vasodilation caused by ATP and ACh but not by hyperoxia, adenosine, or SNP. In the newborn lamb, the pulmonary vasodilating effect of both oxygen and ATP are attenuated by combined P1 and P2y purinergic-receptor antagonists. Postnatally, oxygen-induced pulmonary vasodilation appears to be mediated by ATP through purinergic receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Serine-324 of myosin's heavy chain is photoaffinity-labeled by 3'(2')-O-(4-benzoylbenzoyl)adenosine triphosphate.

A portion of the active site of rabbit skeletal myosin near the ribose ring of ATP can be labeled by the photoaffinity analogue 3'(2')-O-(4-benzoylbenzoyl)adenosine triphosphate (Bz2ATP). The specificity of the photolabeling was assured by first trapping [14C]Bz2ATP at the active site by use of thiol cross-linking agents [Mahmood, R., Cremo, C., Nakamaye, K., & Yount, R. (1987) J. Biol. Chem. 262, 14479-14486]. Five radioactive peptides were isolated by high-performance liquid chromatography after extensive trypsin and subtilisin digestion of photolabeled myosin subfragment 1. Four of these peptides were sequenced by Edman techniques, and all originated from a region with the sequence Gly-Glu-Ile-Thr-Val-Pro-Ser-Ile-Asp-Asp-Gln, which corresponds to rabbit myosin heavy chain residues 318-328. The fifth labeled peptide had an amino acid composition appropriate for residues 312-328. Amino acid composition, radiochemical analysis, and sequence data indicate that Ser-324 is the major amino acid residue photolabeled by Bz2ATP. Spectrophotometric evidence indicates that the benzophenone carbonyl group has inserted into a C-H bond from either the alpha- or beta-carbon of serine. These results place Ser-324 at a distance of 6-7 A from the 3'(2') ribose oxygens of ATP bound at the active site of myosin.

Adenosine Triphosphate↗

Kinetics of phosphate incorporation into adenosine triphosphate and guanosine triphosphate in bacteria.

Escherichia coli cells were labeled with (33)PO(4) for several generations and then (32)PO(4) was added, samples were taken at various times, and adenosine triphosphate (ATP) and guanosine triphosphate (GTP) were purified from an acid extract. The ratio of (32)P/(33)P in each of the six phosphate species was determined and compared to the ratio expected at isotopic steady state. The rate constants of the simplest network of pools which could explain the data, and were consistent with metabolic pathways, were then calculated. In the range of times studied (30 to 3,000 s at 21.5 C) the following generalizations can be made. (i) The gamma-phosphate at ATP requires 2,200 s to achieve 50% of its final specific activity and behaves as if it were exchanging with another species 4.4 times as large, with this other species turning over in 540 s. (ii) The beta-phosphate of ATP and the gamma-phosphate of GTP are in equilibrium with the gamma-phosphate of ATP. (iii) The specific activity of the gamma-phosphate of GTP lags 66 s behind the gamma-phosphate of ATP. (iv) The alpha-phosphates of ATP and GTP have equal specific activities which lag far behind the other four phosphates. A single precursor pool with a turnover time of 416s fits the data best, although a fair fit can be obtained assuming several sequential precursor pools with much shorter turnover times. These findings are consistent with known biosynthetic pathways and the probable flows through them, including the relationship of nucleotide biosynthesis to ribonucleic acid synthesis and turnover.

Adenosine Triphosphate↗

Adenosine triphosphate induces proliferation of human neural stem cells: Role of calcium and p70 ribosomal protein S6 kinase.

Human neural stem cells (NSCs) grown in culture responded to extracellularly applied adenosine triphosphate (ATP), and the rate of proliferation increased as shown by immunocytochemical and RT-PCR analysis. Activation of P2 purinoceptors by ATP is coupled to the release of intracellular calcium ([Ca(2+)](i)) from thapsigargin-sensitive intracellular stores. ATP-induced proliferation was blocked by thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase. Neither EGTA, a calcium chelator, nor caffeine had any effect on ATP-induced [Ca(2+)](i) increases. Multiblot kinase analysis, by which activation of 24 different kinases could be determined, showed that application of ATP to NSCs predominantly activated p70 ribosomal protein S6 kinase (p70 S6 kinase). As well, rapamycin, a p70 S6 kinase inhibitor, blocked the ATP-mediated proliferative response in NSCs. After outlining a role for p70 S6 kinase in ATP-mediated NSC proliferation, we examined the possibility that phosphatidylinositol 3-kinase (PI3-kinase) acts upstream of p70 S6 kinase. The application of wortmannin, a PI3-kinase inhibitor, decreased both ATP-mediated p70 S6 kinase activation and NSC proliferation. From these results, we conclude that ATP application to NSCs induces release of Ca(2+) from intracellular Ca(2+) stores and that this increase in intracellular Ca(2+) in turn promotes NSC proliferation. The increase in NSC proliferation observed following ATP application can also be mediated by PI3-kinase-dependent p70 S6 kinase activation.

Adenosine Triphosphate↗

The adenosine triphosphate test: a bedside diagnostic tool for identifying the mechanism of supraventricular tachycardia in patients with palpitations.

OBJECTIVES: This study assesses the value of the "ATP test" (injection of adenosine triphosphate [ATP] during sinus rhythm) for identifying patients with palpitations of unclear etiology who actually have atrioventricular (AV) nodal re-entry tachycardia (AVNRT) or AV re-entry tachycardia (AVRT). BACKGROUND: Because AVNRT and AVRT can be cured with radiofrequency ablation, documentation of spontaneous AVNRT or AVRT usually prompts referral for electrophysiologic (EP) evaluation. However, these paroxysmal arrhythmias may elude clinical diagnosis. We recently showed that administration of ATP during sinus rhythm often reveals dual AV node physiology or a concealed accessory pathway (AP) in patients with documented AVNRT or AVRT. Thus, we postulated that the ATP test could identify patients with palpitations who actually have AVNRT or AVRT and would therefore benefit from EP evaluation. METHODS: One hundred forty-six patients (54 with "palpitations without documented arrhythmias" and 92 with "documentation of arrhythmias of unclear mechanism") underwent a noninvasive ATP test. ATP was injected during sinus rhythm using 10 mg increments. The ATP test was considered positive when prospectively defined signs of dual AV node physiology or concealed AP were disclosed in the electrocardiogram. These findings were correlated with the results of EP evaluation. RESULTS: A positive ATP test predicted induction of AVNRT or AVRT with a positive predictive value of 93% (sensitivity 71%) but a negative predictive value of 37% (specificity 76%). CONCLUSIONS: A bedside ATP test identifies patients with palpitations who are likely to have AVNRT or AVRT (and who are therefore likely to benefit from EP evaluation) with a high positive predictive value.

Adenosine Triphosphate↗

Vesicular storage of adenosine triphosphate in the guinea-pig cochlear lateral wall and concentrations of ATP in the endolymph during sound exposure and hypoxia.

Previous studies have revealed putative vesicular stores of adenosine triphosphate (ATP) in the marginal cells of the cochlear stria vascularis which may serve as a source of ATP for purinergic signalling. This study aimed to provide further evidence of ATP storage in the cochlea and to see whether ATP levels in the endolymph are affected by noise and hypoxia. Tissues from the lateral wall and organ of Corti of the guinea-pig cochlea were fractionated to obtain vesicular (VF) and mitochondrial (MF) fractions. Free and total ATP were then measured by the luciferase-luciferin reaction from which membrane-bound vesicular ATP was calculated. In the lateral wall, the VF contained 2.02+/-0.04 nmol ATP/mg protein (n = 5), significantly greater (p < 0.001; paired Student's t-test) than the concentration of ATP in the MF (0.36+/-0.05). In the organ of Corti, the VF contained 0.69+/-0.08 nmol ATP/mg protein (n = 4), significantly smaller than the amount in the VF of the lateral wall tissues (p < 0.001; non-paired Student's t-test). Small amounts of fumarase. an enzyme of the mitochondrial matrix, in the VF, excluded the possibility of mitochondrial ATP contamination. To investigate the effect of hypoxia and noise on the ATP concentrations in the endolymph, fluid samples were collected from the first (basal) cochlear turn of anaesthetized guinea-pigs. As a result of hypoxia (15 min, 13% F1O2), ATP concentrations (nM, mean +/- SEM) increased from 6.2+/-2.3 to 9.3+/-4.5 (n = 4), but the difference was not statistically significant. As a result of noise (15 min, 10 kHz, 110 dB SPL. broad band), the ATP levels increased significantly from 7.4+/-1.2 to 16.0+/-1.8 (p = 0.01; Student's t-test: n = 4). This study has demonstrated the presence of a vesicular store of ATP in the stria vascularis of the cochlea and described an increase in the ATP levels in the endolymph during noise exposure. The findings suggest that ATP is actively secreted from the vesicular store under conditions of metabolic stress. The presence of ATP under basal conditions supports a role for ATP in the sound transduction process during normal function.

Adenosine Triphosphate↗

A comparison of the effects of adenosine triphosphate with noradrenaline and with the inhibitory potential of the guinea-pig taenia coli.

1. The response of the smooth muscle of the guinea-pig taenia coli to adenosine triphosphate (ATP) and related substances was compared with that to noradrenaline and dopamine. The effect of these substances on the inhibitory potential was investigated.2. ATP in concentration of 10(-6)-10(-5)M suppressed the spontaneous spike and relaxed the preparation. ATP in a concentration higher than 10(-4)M hyperpolarized the membrane, reduced the membrane resistance and decreased the inhibitory potential.3. Effects of noradrenaline (5 x 10(-6)M) and of dopamine (5 x 10(-4)M) were similar to those of ATP (10(-3)M). However, the effects of catecholamines were reduced in Cl-deficient solution and blocked by phentolamine (3.5 x 10(-6)M), while the effects of ATP were unaffected.4. A high concentration of phentolamine (3.5 x 10(-4)M) almost abolished the inhibitory potential as well as the effects of ATP. The inhibitory potential and the effect of high concentration of ATP (10(-3)M) were not impaired by imidazole (50 mM).5. Adenosine diphosphate, adenosine monophosphate and adenosine produced effects essentially similar to those of ATP. However, their potency was less compared with ATP.6. These electrophysiological observations support the hypothesis that ATP may be the transmitter of the non-adrenergic inhibitory nerves in the taenia coli. No evidence against the hypothesis was obtained.

Action Potentials↗