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Biomedical subjects

T Forrester

Publications and source records attributed to T Forrester.

At least 91 records · Page 5Linked to original sources
PubMed1981

Appearance of adenosine triphosphate in the coronary sinus effluent from isolated working rat heart in response to hypoxia.

1. A working rat heart preparation was used to study the release of adenosine-5'-triphosphate (ATP) into the coronary sinus effluent in response to hypoxia. 2. The left ventricle was set to pump against an hydrostatic pressure of 65 cm water; the left atrial filling pressure was kept constant at 10 cm water. The power output of the heart at these pressures was estimated to be approximately one half of the maximum power development. 3. Samples for ATP assay were collected (a) 30 sec before onset of hypoxia, (b) 60-90 sec after onset of hypoxia, (c) 5 min after restoration of oxygenated buffer solution. Respective concentrations of ATP were (nM +/- S.E.) 0.63 (+/- 0.18), 4.70 (+/- 0.39) and 0.63 (+/- 0.06). The total amounts of ATP detected were (p-mole/min) 5.9 (+/- 0.9), 46.1 (+/- 6.0) and 5.5 (+/- 1.2) respectively. 4. Viability of the hearts was judged to be satisfactory on the following grounds. Alterations in left atrial filling pressure produced typical Frank-Starling responses of the left ventricle. Oxygen extraction from the perfusate increased in response to increased workload. Coronary blood flow increased immediately upon introduction of hypoxic conditions and mechanical recovery from hypoxia was always complete within 5 min of restoring oxygen. 5. In view of the marked extracellular ATPase activity it is concluded that significant vasodilatory concentrations of ATP are released into the myocardial extracellular space in response to hypoxia. A scheme is proposed describing the possible role of adenine nucleotides in the local control of myocardial blood flow.

Adenosine Triphosphate↗
PubMed1979

Effect of adenosine triphosphate and some derivatives on cerebral blood flow and metabolism.

1. Responses of cerebral blood vessels to peri- and intravascular doses of ATP (adenosine triphosphate) and some derivatives were studied in cat and baboon. 2. Perivascular application of ATP to cat pial arterioles gave a threshold dilatory effect at a concentration of 10(-11) M. This figure is comparable to the amount of ATP calculated to be released from electrically stimulated brain slices. 3. It is concluded that adenine nucleotides have a major role to play in the local control of cerebral blood flow. 4. Intracarotid injection of ATP showed a calculated threshold effect at 4 x 10(8) M in the cat and 4 x 10(-9) M in the baboon. 5. The threshold response of the vasculature to intracarotid adenosine lay between 4 x 10(-7) M and 4 x 10(-6) M in the baboon. Little effect was produced with AMP, pyrophosphate and inorganic phosphate. 6. Intracarotid ATP increased the oxygen consumption of the baboon brain parenchyma. This effect was attributed in part to an elevation of the cellular cyclic AMP levels. 7. Osmotic disruption of the blood-brain barrier in baboon did not affect the vasodilatory or metabolic effect of intracarotid ATP. 8. It is postulated that circulating purine compounds mediate a form of metabolic communication inthe body. Also, release of purine compounds from active local nerves might influence cerebral blood flow.

Adenosine Triphosphate↗
PubMed1978

Extracellular nucleotides in exercise: possible effect on brain metabolism.

ATP and other nucleotide derivatives have potent extracellular effects. Sensitive and rapid techniques of ATP detection have shown that ATP is (1) released from active skeletal muscle in vasodilator quantities and (2) released from isolated heart cells in response to hypoxia. Release of nucleotides from active brain tissue has also been demonstrated (Pull and McIlwain, 1972). It is calculated that active cerebral tissue releases sufficient ATP to satisfy local vasodilator requirements in the brain. Intracarotid infusions of ATP have the effect of stimulating oxygen uptake in brain tissue and profoundly increasing the cerebral blood flow. It is not understood how the ATP can exert these effects beyond the blood : brain barrier. Since exercising skeletal muscle releases ATP and other nucleotide derivatives into the circulation, it is postulated that the metabolism of the brain can be significantly affected in exercise. These data, together with the studies by Pritchard et al. (1975) on uptake and supply of purine compounds by the liver, prompt the suggestion that there exists a system of "metabolic communication" in the body mediated by circulating purine compounds.

Adenosine Triphosphate↗
PubMed1977

Release of adenosine triphosphate from isolated adult heart cells in response to hypoxia.

1. Adult rat heart cells were isolated enzymically and ATP was identified in the cell suspension using the firefly luminescence technique. Adenosine 5'-triphosphate (ATP) was not detected from cell suspensions obtained from hearts which had been left asystolic for 10 min.2. It was found that ATP 0.34 +/- 0.22 muM/mg protein was released by cells kept in an oxygenated condition, while ATP 1.28 +/- 0.41 muM/mg protein was initially released by cells made hypoxic.3. Addition of Ca(2+) in a concentration of 2 mM caused cells to initially extrude ATP 0.40 +/- 0.14 muM/mg protein. This was attributed to an inotropic effect.4. Extracellular ATPase activity in the fluid suspension was partially characterized, giving a K(m) of 13 muM and a V/2 of hydrolysed ATP 18.3 muM/min at 37 degrees C. Q(10) was found to be 4 between 25 and 37 degrees C. Enzyme activity remained unaffected by either hypoxic conditions or ouabain.5. If these amounts of ATP are released from myocardial cells rendered hypoxic in vivo, then it must be concluded that ATP plays a principal role in the local control of myocardial blood flow.6. It is proposed that release of ATP occurs through the sarcolemma from an intracellular pool, and that alteration of the configuration of structural membrane protein controls the amounts of ATP extruded.

Adenosine Triphosphatases↗
PubMed1976

Loss of ATP in micromolar amounts after perchloric acid treatment.

Treatment of fluid samples containing known amounts of ATP with 6.0 N perchloric acid (PCA) results in a total loss of 65-71% when the initial concentrations of ATP ranged between 0.5 to 50 muM. Half of this loss was attributed to desensitization of firefly extract (luciferin-luciferase reaction) while the remaining loss was presumably due to adsorption of ATP to perchlorate precipitate upon neutralization. Similar treatment of solutions with higher initial concentrations (100-1000 muM) resulted in apparent total losses averaging 22%. These losses were due solely to desensitization of firefly extract by neutralized PCA. Both the adsorption and desensitization phenomena must be taken into account when the ATP content is measured from tissue extracts and fluid samples subjected to this procedure.

Adenosine Triphosphate↗
PubMed1975

The effect of curare on the release of acetylcholine from mammalian motor nerve terminals and an estimate of quantum content.

Curarized and non-curarized rat hemidiaphragm muscles were indirectly stimulated in vitro. 2. The fluid bathing the active curarized muscles was eluted through a dextran gel (Sephadex G-10), effecting a complete separation of ACh from curare. The acetylcholine fraction was then assayed on an isometric leech muscle preparation. 3. Prostaglandin (PGE1) in a concentration fifteen times that estimated to be released from the skeletal muscle preparation did not affect the response of leech muscle to ACh. 4. The amount of ACh released by curarized muscles (4-9 X 10(-18) mole/impulse-junction) was not significantly different from that released by non-curarized muscles (4-6 X 10(-18) mole/impulse-junction). These quantities are similar to those obtained by previous workers. It is concluded that curare in a paralytic dose does not affect the output of ACh from motor nerve terminals stimulated at low frequencies. 5. Spontaneous release of ACh from non-curarized muscles was estimated at 0-45-0-65 p-mole/min. hemidiaphragm. It is calculated that only 2% of this amount could give rise to post-synaptic electrical events, the remainder having a non-synaptic source. 6. The number of molecules of 'quantal' ACh released by stimulated muscle is calculated as 2-5 X 10(6)/impulse-junction, taking account of the non-synaptic release. The number of ACh molecules in one quantum was estimated to be 6250, an amount that could be easily accommodated in one synaptic vesicle.

Acetylcholine↗
PubMed1972

An estimate of adenosine triphosphate release into the venous effluent from exercising human forearm muscle.

1. Human subjects performed a sustained contraction of the forearm muscles for 4 min in the presence of arterial and venous occlusion.2. The contraction was maintained at 5% of the maximum voluntary contraction, a tension during which the muscle blood flow might be expected to increase by about three times (Lind & McNicol, 1967).3. Adenosine triphosphate (ATP) was identified in the venous effluent from occluded exercising forearm, but not in the venous effluent from occluded forearm without exercise.4. The rate of degradation of ATP was assessed in plasma at 37 degrees C, with an estimate of the percentage loss occurring between sampling and testing. This enabled the rate of appearance of ATP in the blood at the time of exercise to be calculated as approximately 7.5-10.5 mug/min (14-20 n-mole/min). These amounts are compared with 16 mug/min that was infused intra-arterially into human forearm to cause a threefold increase in blood flow (Duff, Patterson & Shepherd, 1954).5. It is likely that the ATP detected in the venous effluent has active muscle as the source; if so, then the amounts calculated to be released could satisfy the vasodilator requirements of active skeletal muscle.6. The effects of circulating ATP on respiration and coronary blood flow during exercise is discussed, including the role it may play locally in the production of ischaemic pain.

Adenosine Triphosphate↗