Characterization of the adenosine receptor responsible for the inhibition of histamine and SRS‐A release from human lung fragments

Hillyard, P.A.; Nials, Anthony T.; Skidmore, I.F.; Vardey, C.J.

doi:10.1111/j.1476-5381.1984.tb16493.x

Cited by 27 publications

(14 citation statements)

References 29 publications

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“…Stanworth, 1983;Nishibori et al, 1983); (2) enhancement by L-N6-phenylisopropyladenosine (L-PIA) is paralleled by its ability to potentiate the early transient rise in adenosine 3': 5'-cyclic monophosphate (cyclic AMP) induced by immunological challenge (Holgate et al, 1980); (3) the 'P-site', inhibitor of adenylate cyclase, 2',5'-dideoxyadenosine (2',5'-DDA), reduces mediator secretion in parallel with its ability to attenuate the IgE-dependent cyclic AMP response (Holgate et al, 1980). Adenosine also modulates histamine release from human mast cells and basophils Hughes et al, 1984;Hillyard et al, 1984) but the characteristics of the effect are different from those of the rat. In rat mast cells, preincubation with adenosine potentiates release whereas in human mast cells and basophils it inhibits, enhancement only occurring with the addition of adenosine at or after the time of challenge.…”

Section: Introductionmentioning

confidence: 99%

Studies on the receptor mediating cyclic AMP‐independent enhancement by adenosine of IgE‐dependent mediator release from rat mast cells

Church

Hughes

Vardey³

1986

British J Pharmacology

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1 Adenosine produced a concentration-related enhancement of antigen-induced 5-hydroxytryptamine (5-HT) release from rat serosal mast cells. This potentiation was maximal following the simultaneous addition of adenosine with antigen. 2 Enhancement of 5-HT release was accompanied by potentiation of the adenosine 3': 5'-cyclic monophosphate (cyclic AMP) response to challenge. The cyclic AMP response, which was antagonized by 8-phenyltheophylline, was characterized as an A2-purinoceptor-mediated effect by the use of 5'-N-ethylcarboxamideadenosine (NECA) and L-N6-phenylisopropyladenosine (L-PIA). 3 Enhancement of 5-HT release, conversely, was not blocked by 8-phenyltheophylline suggesting it to be mediated by a cyclic AMP-independent mechanism. 4 The effect of adenosine on 5-HT release was not reduced by the inhibition of the facilitated uptake of adenosine with dipyridamole, hexobendine or p-nitrobenzylthioguanosine, therefore, suggesting it to be mediated by a cell surface receptor. 5 The receptor mediating enhancement of 5-HT does not appear to belong to the P2-purinoceptor subtype as adenosine was more potent than both adenosine monophosphate (AMP) and adenosine diphosphate (ADP) and xB-methylene ATP was inactive. Furthermore, the effects of AMP were blocked by a,,B-methylene ADP, which inhibits the conversion of AMP to adenosine. 6 Adenosine, NECA, L-and D-PIA were all of equal potency in enhancing 5-HT release. Inosine and 3-deazaadenosine were also active. The rank order of potency of these adenosine analogues is not consistent with an effect at A,-or A2-purinoceptors. 7 There appear to be two adenosine receptors on rat mast cells, an A2-purinoceptor which stimulates adenylate cyclase and a separate purinoceptor, stimulation of which produces enhancement of mediator release by an unknown mechanism. The effects mediated by these receptors appear to be independent of each other.

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Section: Introductionmentioning

confidence: 99%

Studies on the receptor mediating cyclic AMP‐independent enhancement by adenosine of IgE‐dependent mediator release from rat mast cells

Church

Hughes

Vardey³

1986

British J Pharmacology

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“…Adenosine A2 receptors have been reputed to potentiate activation of partially purified dispersed human lung mast cells (4). Inhibition of mast cell activation by adenosine has also been reported in human lung fragments (11), dispersed human lung mast cells (12), and purified lung mast cells (4), depending on the concentration of adenosine used, or the time of incubation. The interpretation of these results, however, can be confounded by the potential indirect effects of adenosine on cell types other than mast cells present in these preparations.…”

Section: Introductionmentioning

confidence: 99%

Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma.

Feoktistov¹,

Biaggioni²

1995

J. Clin. Invest.

335

247

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Adenosine potentiates mast cell activation, but the receptor type and molecular mechanisms involved have not been defined. We, therefore, investigated the effects of adenosine on the human mast cell line HMC-1. Both the A2. selective agonist CGS21680 and the A2./Anb nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased cAMP, but NECA was fourfold more efficacious and had a Hill coefficient of 0.55, suggesting the presence of both A2. and Azb receptors. NECA 10 ,uM evoked IL-8 release from HMC-1, but CGS21680 10 ,uM had no effect. In separate studies we found that enprofylline, an antiasthmatic previously thought to lack adenosine antagonistic properties, is as effective as theophylline as an antagonist of An receptors at concentrations achieved clinically. Both theophylline and enprofylline 300 ,uM completely blocked the release of IL-8 by NECA. NECA, but not CGS21680, increases inositol phosphate formation and intracellular calcium mobilization through a cholera and pertussis toxin-insensitive mechanism. In conclusion, both A2, and A2b receptors are present in HMC-1 cells and are coupled to adenylate cyclase. In addition, Azb receptors are coupled to phospholipase C and evoke IL-8 release. This effect is blocked by theophylline and enprofylline, raising the possibility that this mechanism contributes to their antiasthmatic effects. (J. Clin. Invest. 1995. 96:1979

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“…C3ado is a structural analogue of adenosine and has also been shown to act upon the adenosine receptor causing a small increase of the cyclic AMP levels in different cell types (Zimmerman et al, 1980;Shattil et al, 1982). Adenosine receptors are present in human and guinea-pig lung (Welton & Simko, 1980;Hillyard et al, 1984;Hughes et al, 1984) and accordingly a possible effect of C3ado alone was compared to that of adenosine. In fact, both agents affected differently the contraction and the release of TxB2 induced by antigen, futher dissociating the effect on metabolism and on the receptor(s).…”

Section: Chemicals Andstatistical Analysismentioning

confidence: 99%

Blockade by methylation inhibitors of the anaphylactic response of guinea‐pig lung strips

Randon

Lefort

Vargaftig

1987

British J Pharmacology

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The combination of two methylation inhibitors 3‐deazaadenosine (10−4 or 4 × 10−4 m) plus l‐homocysteine (2 × 10−4 m) caused a time‐dependent inhibition of antigen‐induced contraction, formation of thromboxane B2 (TxB2) and release of histamine from lung parenchyma strips taken from guinea‐pigs actively sensitized with ovalbumin (OA). The methylation inhibitors also prevented the lung strip contractions induced by the mediators platelet‐activating factor (Paf‐acether, 10−6 m), leukotriene D4 (LTD4, 10−8 and 3 × 10−8 m), and in part to arachidonic acid (10−6 and 10−5 m), under conditions where the contractions to histamine (10−6‐10−4 m) were virtually unaffected. TxB2 formation induced by these mediators or by OA was more affected by the methylation inhibitors than the lung strip contractions, indicating that prostaglandin formation is more sensitive to these inhibitors than the myotropic activity. In contrast, the suppressive effect of the methylation inhibitors on histamine secretion by parenchyma lung strips induced by OA followed the inhibition of the contraction. These results show that inhibitors of methyltransferases interfere with the myotropic responses and with the release of mediators by actively sensitized guinea‐pig lung strips stimulated with antigen, and suggest a major role for a methylation process in mediating the contraction of and mediator release by the lung parenchyma.

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Characterization of the adenosine receptor responsible for the inhibition of histamine and SRS‐A release from human lung fragments

Cited by 27 publications

References 29 publications

Studies on the receptor mediating cyclic AMP‐independent enhancement by adenosine of IgE‐dependent mediator release from rat mast cells

Studies on the receptor mediating cyclic AMP‐independent enhancement by adenosine of IgE‐dependent mediator release from rat mast cells

Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma.

Blockade by methylation inhibitors of the anaphylactic response of guinea‐pig lung strips

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