Adenosine; a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils

B. N. Cronstein, Elliot Rosenstein, S. B. Kramer, G. Weissmann, R. Hirschhorn

Research output: Contribution to journalArticle

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Abstract

Adenosine specifically inhibits superoxide anion generation by N-formyl-methionyl-leucyl-phenyl-alanine-stimulated neutrophils without affecting either degranulation or 'aggregation'. We present data that also supports the hypothesis that adenosine engages a specific cell surface receptor to mediate inhibition of stimulated neutrophils. Theophylline (10 and 100 μM), a competitive antagonist at adenosine receptors, reversed the effects of adenosine (0.1 μM) on superoxide anion generation by stimulated neutrophils. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) was a more potent inhibitor of superoxide anion generation than either N6-phenylisopropyladenosine (PIA) or adenosine, an order of potency consistent with that previously demonstrated for adenosine A2 receptors. 2-Chloroadenosine inhibited superoxide anion generation at concentrations similar to NECA. [3H]-NECA and [3H]-2-chloroadenosine bound to a single receptor on intact neutrophils. The characteristics of the receptors for [3H]-NECA and [3H]-2-chloroadenosine were similar [K(d) = 0.22 and 0.23 μM, respectively; number of binding sites = 9.31 and 11.1 x 103 sites/cell, respectively]. NECA, 2-chloroadenosine, adenosine, and PIA inhibited binding of [3H]-NECA with a rank order similar to that for inhibition of superoxide anion generation (NECA = 2-chloroadenosine > adenosine > PIA). There was 50% inhibition of superoxide anion generation by NECA at approximately 20% receptor occupancy. Adenosine, derived from damaged tissues, may serve as a specific, endogenous modulator of superoxide anion generation by activated neutrophils through interaction at this newly described receptor on human neutrophils.

Original languageEnglish (US)
Pages (from-to)1366-1371
Number of pages6
JournalJournal of Immunology
Volume135
Issue number2
StatePublished - Dec 1 1985
Externally publishedYes

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Adenosine-5'-(N-ethylcarboxamide)
varespladib methyl
Superoxides
Adenosine
2-Chloroadenosine
Neutrophils
Phenylisopropyladenosine
leucyl-alanine
Adenosine A2 Receptors
Purinergic P1 Receptor Antagonists
Cell Surface Receptors
Theophylline
Binding Sites

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

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title = "Adenosine; a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils",
abstract = "Adenosine specifically inhibits superoxide anion generation by N-formyl-methionyl-leucyl-phenyl-alanine-stimulated neutrophils without affecting either degranulation or 'aggregation'. We present data that also supports the hypothesis that adenosine engages a specific cell surface receptor to mediate inhibition of stimulated neutrophils. Theophylline (10 and 100 μM), a competitive antagonist at adenosine receptors, reversed the effects of adenosine (0.1 μM) on superoxide anion generation by stimulated neutrophils. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) was a more potent inhibitor of superoxide anion generation than either N6-phenylisopropyladenosine (PIA) or adenosine, an order of potency consistent with that previously demonstrated for adenosine A2 receptors. 2-Chloroadenosine inhibited superoxide anion generation at concentrations similar to NECA. [3H]-NECA and [3H]-2-chloroadenosine bound to a single receptor on intact neutrophils. The characteristics of the receptors for [3H]-NECA and [3H]-2-chloroadenosine were similar [K(d) = 0.22 and 0.23 μM, respectively; number of binding sites = 9.31 and 11.1 x 103 sites/cell, respectively]. NECA, 2-chloroadenosine, adenosine, and PIA inhibited binding of [3H]-NECA with a rank order similar to that for inhibition of superoxide anion generation (NECA = 2-chloroadenosine > adenosine > PIA). There was 50{\%} inhibition of superoxide anion generation by NECA at approximately 20{\%} receptor occupancy. Adenosine, derived from damaged tissues, may serve as a specific, endogenous modulator of superoxide anion generation by activated neutrophils through interaction at this newly described receptor on human neutrophils.",
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Adenosine; a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. / Cronstein, B. N.; Rosenstein, Elliot; Kramer, S. B.; Weissmann, G.; Hirschhorn, R.

In: Journal of Immunology, Vol. 135, No. 2, 01.12.1985, p. 1366-1371.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adenosine; a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils

AU - Cronstein, B. N.

AU - Rosenstein, Elliot

AU - Kramer, S. B.

AU - Weissmann, G.

AU - Hirschhorn, R.

PY - 1985/12/1

Y1 - 1985/12/1

N2 - Adenosine specifically inhibits superoxide anion generation by N-formyl-methionyl-leucyl-phenyl-alanine-stimulated neutrophils without affecting either degranulation or 'aggregation'. We present data that also supports the hypothesis that adenosine engages a specific cell surface receptor to mediate inhibition of stimulated neutrophils. Theophylline (10 and 100 μM), a competitive antagonist at adenosine receptors, reversed the effects of adenosine (0.1 μM) on superoxide anion generation by stimulated neutrophils. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) was a more potent inhibitor of superoxide anion generation than either N6-phenylisopropyladenosine (PIA) or adenosine, an order of potency consistent with that previously demonstrated for adenosine A2 receptors. 2-Chloroadenosine inhibited superoxide anion generation at concentrations similar to NECA. [3H]-NECA and [3H]-2-chloroadenosine bound to a single receptor on intact neutrophils. The characteristics of the receptors for [3H]-NECA and [3H]-2-chloroadenosine were similar [K(d) = 0.22 and 0.23 μM, respectively; number of binding sites = 9.31 and 11.1 x 103 sites/cell, respectively]. NECA, 2-chloroadenosine, adenosine, and PIA inhibited binding of [3H]-NECA with a rank order similar to that for inhibition of superoxide anion generation (NECA = 2-chloroadenosine > adenosine > PIA). There was 50% inhibition of superoxide anion generation by NECA at approximately 20% receptor occupancy. Adenosine, derived from damaged tissues, may serve as a specific, endogenous modulator of superoxide anion generation by activated neutrophils through interaction at this newly described receptor on human neutrophils.

AB - Adenosine specifically inhibits superoxide anion generation by N-formyl-methionyl-leucyl-phenyl-alanine-stimulated neutrophils without affecting either degranulation or 'aggregation'. We present data that also supports the hypothesis that adenosine engages a specific cell surface receptor to mediate inhibition of stimulated neutrophils. Theophylline (10 and 100 μM), a competitive antagonist at adenosine receptors, reversed the effects of adenosine (0.1 μM) on superoxide anion generation by stimulated neutrophils. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) was a more potent inhibitor of superoxide anion generation than either N6-phenylisopropyladenosine (PIA) or adenosine, an order of potency consistent with that previously demonstrated for adenosine A2 receptors. 2-Chloroadenosine inhibited superoxide anion generation at concentrations similar to NECA. [3H]-NECA and [3H]-2-chloroadenosine bound to a single receptor on intact neutrophils. The characteristics of the receptors for [3H]-NECA and [3H]-2-chloroadenosine were similar [K(d) = 0.22 and 0.23 μM, respectively; number of binding sites = 9.31 and 11.1 x 103 sites/cell, respectively]. NECA, 2-chloroadenosine, adenosine, and PIA inhibited binding of [3H]-NECA with a rank order similar to that for inhibition of superoxide anion generation (NECA = 2-chloroadenosine > adenosine > PIA). There was 50% inhibition of superoxide anion generation by NECA at approximately 20% receptor occupancy. Adenosine, derived from damaged tissues, may serve as a specific, endogenous modulator of superoxide anion generation by activated neutrophils through interaction at this newly described receptor on human neutrophils.

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