Abstract |
In vitro studies in rat mastocytes and human monocytes suggested that reproterol (a selective beta(2)- adrenoceptor agonist with a theophylline moiety) exerts anti-inflammatory actions through inhibition of cyclic AMP (cAMP) PDE activity. Thus, reproterol was tested for its ability to inhibit cAMP PDE in cultured mouse mastocytoma P-815 cells. cAMP PDE activity was measured in intact cells by spectrofluorometry using the fluorescent substrate 2'-O-anthraniloyl cAMP. Reproterol was more potent than theophylline to inhibit cAMP PDE (pIC(50)=4.28+/-0.25 vs. 3.16+/-0.05). This contrasted with disrupted cells, where the PDE inhibitory potency of reproterol was low (pIC(50)=2.85+/-0.03) and similar to that of theophylline (pIC(50)=2.66+/-0.19). No cAMP PDE inhibition was found with other beta(2)-agonists tested ( fenoterol, salbutamol, salmeterol and formoterol). Finally, the selective PDE inhibitors calmidazolium (100 nM), milrinone (5 microM) and rolipram (50 microM) inhibited cAMP PDE activity by approximately 20, 30 and 25% respectively. In conclusion, reproterol potently and non-specifically inhibited intracellular cAMP phosphodiesterases in intact mastocytoma cells. This can explain the previously reported beta(2)-adrenoceptor-independent anti-inflammatory actions of reproterol in vitro. Further studies are required to define the anti-inflammatory potential of reproterol in asthma.
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Authors | M Alvarez-Guerra, H Libertus, R P Garay |
Journal | Pulmonary pharmacology & therapeutics
(Pulm Pharmacol Ther)
Vol. 17
Issue 4
Pg. 213-8
( 2004)
ISSN: 1094-5539 [Print] England |
PMID | 15219266
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Adrenergic beta-Agonists
- Bronchodilator Agents
- Drug Combinations
- Phosphodiesterase Inhibitors
- reproterol
- Metaproterenol
- Theophylline
- Cyclic AMP
- 3',5'-Cyclic-AMP Phosphodiesterases
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Topics |
- 3',5'-Cyclic-AMP Phosphodiesterases
(antagonists & inhibitors, metabolism)
- Adrenergic beta-Agonists
(administration & dosage, pharmacology)
- Animals
- Bronchodilator Agents
(administration & dosage, pharmacology)
- Cyclic AMP
(antagonists & inhibitors)
- Dose-Response Relationship, Drug
- Drug Combinations
- Metaproterenol
(administration & dosage, analogs & derivatives, pharmacology)
- Mice
- Phosphodiesterase Inhibitors
(administration & dosage, pharmacology)
- Theophylline
(administration & dosage, analogs & derivatives, pharmacology)
- Tumor Cells, Cultured
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