The Fate of Adenine Nucleotides in the Pulmonary Circulation of Isolated Lung

Chelliah, Rajani; Bakhle, Y.S.

doi:10.1113/expphysiol.1983.sp002724

Cited by 10 publications

(6 citation statements)

References 10 publications

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“…Firstly, the efflux of radioactivity in lung effluent following infusion of [3H]-adenosine, while being rapid, was still slower than that following infusion of [3H]-ADP. This was expected since ADP, which is metabolized Table 3 extensively to AMP (Chelliah & Bakhle, 1983) by membrane-bound enzymes, has a pulmonary transit time comparable with that of the vascular marker ['4C]-dextran (Crutchley, Eling & Anderson, 1978) because both substrate and product are nucleotides and thus excluded from cells. Adenosine, on the other hand, is known to be taken up by endothelial and smooth muscle cells where it may be attacked by intracellular adenosine deaminase and nucleoside phosphorylase (Rubio, Wiedmeier & Berne, 1972) to yield inosine and hypoxanthine respectively and by kinases to form adenine nucleotides (Pearson et al, 1978).…”

Section: Discussionmentioning

confidence: 96%

“…The efflux profile for ADP has been taken from our previous work (Chelliah & Bakhle, 1983 the lowest curve).…”

Section: Efflux Of Radioactivitymentioning

confidence: 99%

“…Because lung effluent had been shown to exhibit ADP-ase activity (Chelliah & Bakhle, 1983), in three experiments adenosine (10 Mm and 1 mM) was incubated with samples of effluent collected from lung and with Krebs solution which had not been perfused through lung, for up to 4 h at 37°C. At 1 mM, 94 ± 1.0% and at 10 gM, 84 ± 0.3% of the adenosine was recovered unchanged after 4 h incubation with lung effluent compared with 95 % recovery after an equivalent incubation with Krebs solution alone.…”

Section: Analysis Of Effluent Radioactivitymentioning

confidence: 99%

“…The efflux profile for ADP has been taken from our previous work (Chelliah & Bakhle, 1983. Following [3H]-adenosine infusions, efflux of 3H was rapid; at 10 jiM (the uppermost curve), 90%o of the 3H appearing in 15 mmn had been collected in the first minute's fractions.…”

Section: Efflux Of Radioactivitymentioning

confidence: 99%

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Metabolism and uptake of adenosine in rat isolated lung and its inhibition

Bakhle

Chelliah

1983

British J Pharmacology

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1 The metabolism of adenosine perfused through the pulmonary circulation of isolated lungs from rats was investigated radiochemically. 2 Following a lOs infusion of radioactive ['4C]-or [3H]-adenosine, the recovery of radioactivity in effluent from the lung after 1 min increased from 30% at 0.5 JAM to 80% at 1 mM adenosine. 3 Unchanged adenosine comprised the major radioactive species in effluent, being about a third of the total up to 100 IAM. 4 Uptake of radioactivity was saturable at high concentrations with an apparent Km of 215 AM. 5Radioactivity retained in lung comprised over 80% as ATP and about 2% as adenosine at all concentrations. 6 Perfusion of lungs with Krebs solution containing dipyridamole (1-100 MM) or adenine (10 JM) increased the rate of radioactive efflux, decreased uptake of radioactivity by lung and decreased metabolites of adenosine (inosine and hypoxanthine) in the effluent.7 Dipyridamole (10 ltM) was more potent in decreasing uptake in guinea-pig lungs than in rat lungs. 8 From these results we conclude that the pulmonary circulation in rat lung exhibits a significant inactivation process for adenosine. The isolated lung provides a convenient preparation for studying in situ pharmacological or pathological modifications of this vascular inactivation process.

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Section: Discussionmentioning

confidence: 96%

“…The efflux profile for ADP has been taken from our previous work (Chelliah & Bakhle, 1983 the lowest curve).…”

Section: Efflux Of Radioactivitymentioning

confidence: 99%

Section: Analysis Of Effluent Radioactivitymentioning

confidence: 99%

Section: Efflux Of Radioactivitymentioning

confidence: 99%

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Metabolism and uptake of adenosine in rat isolated lung and its inhibition

Bakhle

Chelliah

1983

British J Pharmacology

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“…The composition of the effluent radioactivity was then analysed by collecting lung effluent in a single 1 min fraction and separating the radioactive species by t.l.c. (Chelliah & Bakhle, 1983).…”

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confidence: 99%

Proceedings of the Physiological Society, 28‐29 March 1985, University College London Meeting: Communications

1985

The Journal of Physiology

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We have previously shown that the Lambert-Eaton myasthenic syndrome (L.E.M.S.) is an autoimmune disorder (Lang, Newsom-Davis, Prior & Wray, 1983). IgG autoantibodies interfere with release of acetylcholine from presynaptic nerve terminals of the skeletal neuromuscular junction. The experiments reported here were designed to investigate the mechanism of action of these antibodies at depolarized nerve terminals.Mice were injected with control or L.E.M.S. IgG (30 mg/day, i.P.) for 2 days, and the diaphragm muscle removed on the third day, as previously described (Lang et al. 1983). Miniature end-plate potentials (m.e.p.p.s) were recorded using microelectrodes in Krebs solution (23-26 'C) containing high K+ concentration (15-9 mM) and a range of Ca2+ concentrations (0-25-2-5 mm).In controls, m.e.p.p. frequency increased with Ca2+ concentration from a value of 5 03 + 0 69 s-1 (n = 19 end-plates) at 0-25 mM-Ca2+ concentration to a plateau value of 79-3 + 6-8 s-1 (n = 18) at 1-5 mM-Ca2+ concentration. Further increase in Ca2+ concentration produced no further increase in this plateau value. The curve of m.e.p.p. frequency versus Ca2+ concentration for L.E.M.S. IgG-treated animals was similar in shape to that for controls, but with significantly reduced (P < 0-002) m.e.p.p. frequency values at all Ca2+ concentrations. The extent of these reductions was to 34 46 % of control values. Thus the curve was shifted to the right with a reduced plateau. The plateau value of m.e.p.p. frequency was reached at similar Ca2+ concentrations as for controls but was reduced to 36-4 + 4-9 s51 (n = 19, Ca2+ concentration = 1-5 mM).These reductions in m.e.p.p. frequency at potassium-depolarized nerve terminals by L.E.M.S. IgG indicate that it is unlikely that this antibody acts solely (if at all) on action potential mechanisms, since no action potentials were involved in the present experiments. On the other hand, voltage-dependent Ca2+ channels would be expected to be opened by the depolarization produced under the above experimental conditions. L.E.M.S. IgG may act on these latter channels to cause their loss of function as suggested previously (Lang, Newsom-Davis, Prior & Wray, 1984). The present results are consistent with such an action, and the reduced plateau value of the above curve produced by the L.E.M.S. IgG shows further that the mechanism is not one of competitive antagonism.

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Ectonucleotidases

Pearson

1985

Methods Used in Adenosine Research

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The Fate of Adenine Nucleotides in the Pulmonary Circulation of Isolated Lung

Cited by 10 publications

References 10 publications

Metabolism and uptake of adenosine in rat isolated lung and its inhibition

Metabolism and uptake of adenosine in rat isolated lung and its inhibition

Proceedings of the Physiological Society, 28‐29 March 1985, University College London Meeting: Communications

Ectonucleotidases

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