Inhibition of mast cell adenosine responsiveness by chronic exposure to adenosine receptor agonists

Marquardt, Diana L.; Walker, Linda L.

doi:10.1016/0006-2952(87)90674-5

Cited by 15 publications

(7 citation statements)

References 13 publications

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“…Tachyphylaxis of the potentiation of 5-HT release by adenosine from rat mass cells has been reported previously (Church et al, 1986). Marquardt & Walker (1987) also reported that adenosineinduced potentiation of IgE-stimulated granule-derived P-hexosaminidase release is markedly attenuated by prior exposure to the A2-receptor agonist, N'ethylcarboxamideadenosine. The bronchoconstrictor response of atopic mildly asthmatic subjects to the related nucleotide AMP, which is used as a precursor for adenosine, was also attenuated on repeated exposure (Phillips et al, 1989).…”

Section: Discussionsupporting

confidence: 59%

Adenosine‐induced bronchoconstriction of isolated lung and trachea from sensitized guinea‐pigs

Thorne

Broadley

1992

British J Pharmacology

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1 The bronchoconstriction of airway-perfused lungs and contraction of superfused tracheal spirals from guinea-pigs in response to adenosine were examined. 2 In lungs from untreated animals, adenosine had little effect unless the perfusion pressure was raised with carbachol (1.1 tlM), when it caused a fall in perfusion pressure. However, if removed from guinea-pigs sensitized with ovalbumen (5 mg and 10 mg i.p. 14 and 12 days before use), adenosine was bronchoconstrictor, exerting bronchodilator effects only at high (1 mg) doses. The constrictor response to adenosine (300 lig) was significantly greater than that in lungs from untreated or sham-injected animals. 3 In superfused trachea from untreated animals, adenosine exerted only relaxant responses. In tissues from ovalbumen-sensitized guinea-pigs adenosine produced contracile responses, with relaxation appearing only at high (1 mg) doses. 4 Thus sensitization by antigen challenge revealed a bronchoconstrictor response of isolated airway preparations to adenosine. This is related to the clinical situation where only asthmatic subjects respond to adenosine by bronchoconstriction and suggests that the sensitization may destabilize inflammatory cells for mediator release by adenosine. 5 The response to a second exposure to adenosine was consistently reduced (lungs) or converted to a relaxation (trachea) indicating tachyphylaxis and consistent with a mediator release mechanism. 6 The P,-purinoceptor antagonist, 8-phenyltheophylline (3.9 jiM), antagonized the relaxant responses to higher doses of adenosine. However, it did not affect the contractile responses to lower doses of adenosine. Whether this is due to P,-purinoceptors not being involved in the contractile response, or whether preferential blockade of the relaxant response leaves the contraction unopposed and apparently unblocked, remains to be established. Keywords: Adenosine; airway perfused lungs of guinea-pig; superfused trachea; bronchoconstriction; ovalbumen sensitization IntroductionThe predominant response of airway smooth muscle to adenosine is relaxation (Farmer & Farrar, 1976;Karlsson et al., 1982;Darmani & Broadley, 1986) which is mediated via P,-purinoceptors of the A2-subtype (Brown & Collis, 1982). In human non-asthmatic subjects, however, adenosine has no effect upon pulmonary function (Cushley et al., 1983) while in asthmatics it produces a bronchoconstriction (Cushley et al., 1983;Crimi et al., 1988;1989 (Satchell & Smith, 1984). The small contractile component precedes the predominant relaxation (Coleman, 1976;Karlsson et al., 1982) and appears to depend upon the degree of resting tone (Fredholm et al., 1979;Advenier et al., 1982). There is some Author for correspondence. disagreement regarding whether the contractile response to the adenosine analogue L-N6-phenylisopropyladenosine (L-P1A) is antagonized by PI-receptor antagonists (Caparrotta et al., 1984;Ghai et al., 1987;Farmer et al., 1988). However, the possibility exists for it being mediated via the release of arachidonic acid derivat...

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Section: Discussionsupporting

confidence: 59%

Adenosine‐induced bronchoconstriction of isolated lung and trachea from sensitized guinea‐pigs

Thorne

Broadley

1992

British J Pharmacology

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“…A second possibility is that the adenosine released during mast cell activation is too rapidly metabolized to allow the necessary exposure time to induce receptor desensitization. In our previous studies of receptor desensitization, the presence of deoxycoformycin, an inhibitor of adenosine deaminase, was necessary to produce receptor desensitization [9]. It is likely that both these explanations for the failure of adenosine receptors to desensitize after immunologic challenge are true.…”

Section: Discussionmentioning

confidence: 91%

“…The mechanism of this observed secretogogue-specific desensitization remains unclear, although some type of uncoupling of the receptors from relatively early steps in the secretory process may be hypothesized. Mast cells may be made transiently unresponsive to adenosine and related agents by an initial exposure to an adenosine receptor agonist [9]. The mechanism of this receptor desensitization is poorly understood but may involve receptor internalizaton or uncoupling from a G protein linkage.…”

Section: Discussionmentioning

confidence: 98%

“…Mast cells respond to exogenous adenosine with a marked enhancement or ongoing mediator release [6]. Adenosine appears to bind to cell surface receptors that may be up-regulated by chronic exposure to receptor antagonists such as aminophylline [1][2][3][4][5][6][7] or the corticosteroid dexamethasone [8] or may be down-regulated and/or desensitized by exposure to adenosine receptor agonists such as N-ethylcarboxamidoadenosine (NECA) [9]. The precise mechanisms underlying these receptor regulatory processes are as yet unclear, although an increase in adenosine receptor number as assessed by radioligand binding has been documented in the case of up-regulation.…”

Section: Introductionmentioning

confidence: 99%

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Mast cell desensitization to IgE fails to induce a parallel adenosine receptor desensitization

1993

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Desensitization induced by challenge of mast cells with antigen is specific for IgE-dependent signals. During the secretory process mast cells release adenosine, which can induce a desensitization of adenosine receptors. To determine whether adenosine receptors may be desensitized from a previous antigen challenge, mast cells were sensitized with anti-DNP IgE antibody, challenged with DNP-BSA antigen, returned to culture overnight, resensitized, and rechallenged. Previously challenged cells exhibited increased spontaneous beta-hexosaminidase release, but adenosine retained its ability to augment beta-hexosaminidase release. Adenosine enhanced A23187-stimulated release of beta-hexosaminidase in control and previously challenged cells. Leukotriene C4 generation followed a similar pattern. Mastoparan, a direct G protein activator and mast cells secretagogue, produced a doubling of beta-hexosaminidase release in previously challenged cells. Results using other G protein activators were equivocal. Degranulation alone is insufficient to induce adenosine receptor hyposensitization. Whether the hyperresponsiveness to mastoparan is a consequence of uncoupling of IgE receptors from G proteins remains uncertain.

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“…The first report about desensitization to adenosine was in neuroblastoma cells in tissue culture (Green, 1977), although a clear demonstration of this phenomenon was also reported by McNeal et al (1980) in guinea-pig cerebral cortex. Desensitization to adenosine has been reported in different tissues such as hippocampus (Lee et al, 1986;Porter et al, 1988), striatum (Porter et al, 1988;Abbracchio et al, 1992;), neocortex (McNeal et al, 1980Porter et al, 1988;Abbracchio et al, 1993), locus coeruleus (Regenold & Illes, 1990), neuroblastoma (Kenimer & Nirenberg, 1981;Kelly et al, 1990), liver (Buxton et al, 1987), kidney (Newman & Levitzki, 1983), smooth muscle (Hayashi et al, 1985;Ramkumar et al, 1991), vascular smooth muscle (Anand-Strivastava et al, 1989;Hussain & Mustafa, 1993), heart or myocytes (Shryock et al, 1989;Liang & Donovan, 1990), endothelial cells (Luty et al, 1989), mast cells (Marquardt & Walker, 1987), adipocyte cells (Parsons & Stiles, 1987;Hoffman et al, 1989;Longabaugh et al, 1989;Stoneham, 1989). Adenosine desensitization was seen both in vivo (Lee et al, 1986) and in vitro (Abbracchio et al, 1992).…”

Section: Desensitizationmentioning

confidence: 99%

The effect of calcium removal on the suppression by adenosine of epileptiform activity in the hippocampus: demonstration of desensitization

Hosseinzadeh

Stone

1994

British J Pharmacology

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1 Previous work has suggested that presynaptic effects of adenosine may be dependent on divalent cations. The present study was undertaken to determine whether a similar requirement existed at postsynaptic sites. 2 Extracellular recordings were made in the CAl pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum or antidromic stimulation of the alveus. In antidromic stimulation experiments, CaC12 was omitted (calcium-free medium) or reduced to 0.24 mM (low calcium medium) and in some experiments MgSO4 was increased to 2 mM. Kynurenic acid at concentrations of 1 and 5 mM in calcium-free medium and 1 mM in low calcium medium had no effect on secondary spike size. 3 Adenosine and baclofen induced a concentration-dependent reduction in the amplitude of orthodromic potentials with maximum effects at 20 and 5 gLM respectively. 4 In nominally calcium-free medium, bursts of multiple population spikes were obtained in response to antidromic stimulation. Adenosine had little effect in reducing the secondary spike amplitude. At high concentration (2 mM) an initial depression was seen which declined within 3-5 min. 5 Sensitivity to adenosine was restored in low calcium medium or by raising magnesium. Although raising the divalent cation concentration increased the inhibitory effect of adenosine, desensitization was still seen. 6 2-Chloroadenosine (100-500 JAM) and R-PIA (501AM), which are not substrates for either the nucleoside transporters or adenosine deaminase, were inactive in the absence of calcium. S-(2-hydroxy-5 nitrobenzyl)-6-thioinosine, an adenosine uptake blocker, at a concentration 100 JM had no effect on secondary potential size and did not restore adenosine sensitivity in calcium-free medium. 7 Thapsigargin, which discharges intracellular calcium stores, had no significant effect at 1 JAM on the bursts of action potentials and did not change the effect of 0.5 mM adenosine in calcium-free medium. 8 Unlike adenosine, baclofen concentration-dependently reduced the secondary spike size in calciumfree medium and no sign of recovery was observed during maintained superfusion for up to 45 min. No cross-desensitization was seen between baclofen and adenosine. 9 Applications of adenosine locally by pressure to neuronal somata or dendrites still resulted in desensitized responses in calcium-free medium. 10 It is concluded that the postsynaptic sensitivity to adenosine is dependent on the concentration of divalent cations in the extracellular space implying an effect of cations on adenosine receptor activation or transduction processes.

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Inhibition of mast cell adenosine responsiveness by chronic exposure to adenosine receptor agonists

Cited by 15 publications

References 13 publications

Adenosine‐induced bronchoconstriction of isolated lung and trachea from sensitized guinea‐pigs

Adenosine‐induced bronchoconstriction of isolated lung and trachea from sensitized guinea‐pigs

Mast cell desensitization to IgE fails to induce a parallel adenosine receptor desensitization

The effect of calcium removal on the suppression by adenosine of epileptiform activity in the hippocampus: demonstration of desensitization

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