Adenosine-induced bronchoconstriction in conscious hyperresponsive and sensitized guinea pigs.

Thorne, Julian R.; Broadley, Kenneth J.

doi:10.1164/ajrccm.149.2.8306036

Cited by 32 publications

(33 citation statements)

References 31 publications

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“…Non-invasive measurement of specific airways conductance Specific airways conductance (sGaw) was determined using constant volume, whole body plethysmography in unanaesthetized spontaneously breathing guinea-pigs (Agrawal, 1981;Griffiths-Johnson et al, 1988;Thorne & Broadley, 1994). Each animal was fitted with a face mask and placed in a restrainer which was then slid into the plethysmograph chamber.…”

Section: Effect Of Atropinementioning

confidence: 99%

“…Similarly, isolated lung tissues from sensitized guinea-pigs show a constrictor response to adenosine whereas tissues from unsensitized animals display the more usual direct smooth muscle relaxant effects mediated via A2 receptors (Thorne & Broadley, 1992). The bronchoconstrictor responses to adenosine or 5'-AMP in whole animals (Thorne & Broadley, 1994) human subjects (Phillips et al, 1989) and isolated tissues (Thorne & Broadley, 1992) are rapidly tachyphylactic. Thus, in the present experiments the exposures to adenosine were placed 8 days apart, (the ovalbumin exposure being given on day 7).…”

Section: Effect Of Atropine On S-ht-and Mch-induced Bronchoconstrictionsmentioning

confidence: 99%

“…Non-surgical plethysmographic techniques allow the longterm or repeated measurement of lung function in conscious animals under minimal restraint (Amdur & Mead, 1958;Griffiths-Johnson et al, 1988;Ball et al, 1991;Thorne & Broadley, 1994). The technique developed by Griffiths-Johnson et al (1988) is the basis of the method used in this study.…”

Section: Introductionmentioning

confidence: 99%

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Airway hyper‐ or hyporeactivity to inhaled spasmogens 24 h after ovalbumin challenge of sensitized guinea‐pigs

Lewis

Broadley

1995

British J Pharmacology

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1 The aim of this study was to determine whether an inhalation of ovalbumin (OA, 10 or 20 mg ml-') by conscious OA-sensitized guinea-pigs leads to airway hyperreactivity to spasmogens 24 h later. In contrast to most previous studies, the spasmogens (5-HT, methacholine (MCh), U-46619 and adenosine) were administered by inhalation and airway function was measured in conscious guinea-pigs. 2 Guinea-pigs were sensitized by i.p. injection of 10 jg OA and 100 mg aluminium hydroxide in 1 ml normal saline; 14-21 days later they were exposed to an inhalation of 5-HT, MCh, U-46619 or adenosine. Specific airway conductance (sGaw) was measured in conscious animals by whole body plethysmography. The spasmogens caused bronchoconstriction, measured as a reduction in sGaw from the pre-inhalation basal values. Dose-related bronchoconstrictions were observed with 5-HT, MCh and U-46619. 3 The effect of an ovalbumin macroshock challenge upon the responses to each spasmogen were examined by giving an inhalation of aerosolized OA at 24 h (or 7 days in the case of adenosine) after an initial spasmogen challenge. Eighteen to twenty-four hours after the OA macroshock, the same guineapigs were exposed to a repeated inhalation of 5-HT, MCh, U-46619 or adenosine. 4 U-46619 was the only spasmogen to demonstrate hyperresponsiveness, the peak change in sGaw being increased from -12.3 + 9.9 to -38.8 + 5.0% by 10 mg ml-' OA challenge. In contrast, the ovalbumin challenge (20 mg ml-') inhibited the bronchoconstrictions to 5-HT (50 jg ml-') and MCh (100 jig ml-'). Adenosine demonstrated bronchoconstriction in sensitized guinea-pigs but no significant change in the response was observed after an OA challenge. 5 All results were compared with a control group of sensitized guinea-pigs receiving a NaCl challenge. The bronchoconstrictor responses to 5-HT, MCh, U-46619 or adenosine did not differ significantly before and after the saline challenge, indicating reproducibility of the responses. 6 In further experiments, guinea-pigs were exposed to inhalation of 5-HT (50 jg ml-') or MCh (300 jg ml-') 24 h before atropine (10 jig, 100 jg or 1 mg ml-') and again at 0.5 to 1.5 h afterwards. Atropine antagonized the 5-HT-and MCh-induced bronchoconstrictions over the same antagonist doserange. This suggests that the bronchoconstriction induced in the conscious guinea-pig by 5-HT is mediated primarily via muscarinic receptors, possibly by a vagal reflex. The inhibition of the responses to 5-HT and MCh by OA challenge would therefore appear to be related to interference with a common cholinergic pathway for these spasmogens. 7 In summary, airway hyperresponsiveness was evident at 24 h after OA challenge as measured by an enhanced bronchoconstrictor response to inhaled U-46619. When 5-HT or MCh were used as the spasmogens, an opposing decrease in responsiveness was observed. This was presumed to be due to an inhibition of cholinergic pathways by the OA challenge. Adenosine caused a bronchoconstriction in the sensitized animals but this was not enhanced by the OA ...

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Section: Effect Of Atropinementioning

confidence: 99%

Section: Effect Of Atropine On S-ht-and Mch-induced Bronchoconstrictionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Airway hyper‐ or hyporeactivity to inhaled spasmogens 24 h after ovalbumin challenge of sensitized guinea‐pigs

Lewis

Broadley

1995

British J Pharmacology

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“…In guinea pigs, nebulized adenosine produces bronchoconstriction similar to that in the humans (26,27). Bronchoconstriction occurs in adenosine-perfused guinea pig lung and this adenosine response is enhanced by sensitization to ovalbumin (28).…”

Section: Walkermentioning

confidence: 93%

Effects of adenosine on guinea pig pulmonary eosinophils

Walker

1996

Inflammation

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Extracellular adenosine has pharmacological activity on a wide variety of cell types and may play an important role as an inflammatory modulator with both pro- and anti-inflammatory activities. These studies examine the effects of adenosine on guinea pig pulmonary eosinophils. Adenosine alone did not directly induce superoxide (O2-) production. Pretreatment with adenosine primed the O2- response of guinea pig pulmonary eosinophils following the addition of 1 or 10 microM platelet-activating factor (PAF). Priming was seen at adenosine concentrations greater than 1 microM and was maximal at 100 microM. At this maximal dose, adenosine priming increased the O2- response to 1 microM and 10 microM PAF by 86% and 51%, respectively. Priming by adenosine was not seen when ionomycin or phorbol myristate acid (PMA) were used as agonists. In fura-2 loaded eosinophils, the addition of 100 microM adenosine resulted in a small but significant rise in intracellular calcium of 54.4 +/- 9.2 nM above baseline. In contrast, similar adenosine concentrations had no effect on cytosolic calcium levels in guinea pig neutrophils. These data demonstrate a pro-inflammatory role for adenosine in elicited guinea pig pulmonary eosinophils.

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“…Adenosine metabolism in the lung has been examined mainly in the context of asthma [8], where it was shown to induce bronchoconstriction. In contrast, adenosine is virtually inactive in non-asthmatics.…”

Section: Introductionmentioning

confidence: 99%

Evidence for, and characterization of, a lipopolysaccharide‐inducible adenosine A2 receptor in human tracheal gland serous cells

1995

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Human tracheal glands are considered as the principle secretory structures in the bronchotracheal tree. In earlier studies, we successfully performed primary cultures of human tracheal gland (HTG) serous cells and noted that these cells were responsive to many secretagogues including purinergic agonists but not to the inflammatory mediator adenosine. In this study, we demonstrate that adenosine was capable of inducing stimulation of protein secretion by HTG serous cells which had previously been cultured in pro-inflammatory conditions (induced by lipopolysaccharide (LPS)).

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Adenosine-induced bronchoconstriction in conscious hyperresponsive and sensitized guinea pigs.

Cited by 32 publications

References 31 publications

Airway hyper‐ or hyporeactivity to inhaled spasmogens 24 h after ovalbumin challenge of sensitized guinea‐pigs

Airway hyper‐ or hyporeactivity to inhaled spasmogens 24 h after ovalbumin challenge of sensitized guinea‐pigs

Effects of adenosine on guinea pig pulmonary eosinophils

Evidence for, and characterization of, a lipopolysaccharide‐inducible adenosine A2 receptor in human tracheal gland serous cells

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