Mechanisms of Xanthine Actions in Models of Asthma

Howell, R E; Gaudette, R. F.; Raynor, Mathew C.; Warner, A. T.; Muehsam, W. T.; Schenden, J A; Perumattam, John; Hiner, Roger N.; Kinnier, William J.

doi:10.1007/978-1-4612-3400-5_54

Cited by 2 publications

(1 citation statement)

References 19 publications

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“…Structures of R 75231 (20), an analog of the adenosine uptake inhibitor, mioflazine; the binding enhancer PD 81,723 (21); and 5-amino-4-imidazole carboxamide (AICA) riboside (22). Table 1 Potential therapeutic uses of drugs acting at adenosine receptors [1,[7][8][9][10][11][12][13][14][15][16] Structures of selected adenosine agonists and affinities at A 1 -and A 2 -adenosine receptors (data from references given in text) Table 3 Summary of the receptor-mediated * renal effects of adenosine …”

Section: Resultsmentioning

confidence: 99%

Novel therapeutics acting via purine receptors

Jacobson

Trivedi²,

Churchill

et al. 1991

Biochemical Pharmacology

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A recent conference entitled Purines in Cell Signalling: Targets for New Drugs, held in Rockville, Maryland, in September, 1989, was one indication of the increasing interest in developing agonists and antagonists of P 1 -(adenosine) and P 2 -(ATP) purinoceptors [1] as potential therapeutic agents. Extracellular adenosine, acting at its membrane bound A 1 and A 2 receptors, is a ubiquitous modulator of cellular activity. The purine can arise from several sources including ATP hydrolysis by ectokinase activity in the region of the nerve terminal [2] and from S-adenosylhomocysteine [3] and ATP within the cell. Together with its more stable analogs, adenosine is a potent inhibitor of neurotransmitter release in both the central and peripheral nervous systems, and in cardiac, adipose and other tissues. Adenosine can also affect blood pressure and heart rate as well as modulate the function of the immune, inflammatory, gastrointestinal, renal and pulmonary systems, either via its effects on transmitter release or directly via receptor mechanisms altering intracellular transduction processes.

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Section: Resultsmentioning

confidence: 99%

Novel therapeutics acting via purine receptors

Jacobson

Trivedi²,

Churchill

et al. 1991

Biochemical Pharmacology

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Activation of A3 adenosine receptors on human eosinophils elevates intracellular calcium

Kohno

Mawhorter

et al. 1996

Blood

111

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Adenosine (ADO) is a potent bronchoconstrictor in allergic patients and has been shown to increase the release of histamine from human lung tissues. Antagonists of ADO A1 and A2A receptors are not effective in attenuating these effects. Therefore, involvement of ADO A3 receptors in the bronchoconstrictor and/or inflammatory effects have to be considered. Eosinophils also play a pivotal role in allergic diseases such as asthma, thus it is natural to consider a link between the A3 receptor and eosinophils. Human peripheral blood eosinophils express the ADO A3 receptor as indicated by detection of the transcript for A3 receptors in polymerase chain reaction-amplified cDNA derived from the cells. A3 receptors on eosinophil membranes were characterized using the A3 receptor agonist radioligand 125I-labeled AB-MECA, which yielded Bmax and Kd values of 1.31 pmol/mg protein and 3.19 nmol/L, respectively. Treatment of eosinophils with the highly potent and selective A3 receptor agonist CI-IB-MECA clearly induced Ca2+ release from intracellular Ca2+ pools followed by Ca2+ influx, suggesting the presence of phospholipase C-coupled A3 receptors. In contrast, the ADO receptor agonists CPA and CGS 21680, selective for A1 and A2A receptors, respectively, at concentrations of < or = 30 mumol/ L did not elevate the intracellular Ca2+ level. These results attest to the existence of ADO A3 receptors on eosinophils and suggest that ADO stimulates these cells to release Ca2+ from intracellular stores via the activation of A3 receptors.

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Mechanisms of Xanthine Actions in Models of Asthma

Cited by 2 publications

References 19 publications

Novel therapeutics acting via purine receptors

Novel therapeutics acting via purine receptors

Activation of A3 adenosine receptors on human eosinophils elevates intracellular calcium

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