Abstract |
The effect of rolipram, an isozyme IV-selective inhibitor of cAMP-specific phosphodiesterase, was evaluated in a guinea pig eye model of tissue eosinophilia. (R)- rolipram was administered by gavage to guinea pigs 1 h prior to topical ocular challenge with a mixture of leukotrienes (LTs) (10 ng LTB4 + 1000 ng LTD4/eye) or with histamine dihydrochloride (1 mg/eye). Conjunctivae were evaluated histologically 6 h after challenge. Eosinophil counts per millimeter of conjunctival epithelium in LT-challenged animals that received (R)- rolipram at dosages of 0.1, 0.3, 1, 3, or 10 mg/kg were reduced by 63, 63, 84, 81 and 90% respectively, compared to LT-challenged controls. Reduction was statistically significant (P < 0.05) at all dosages. Eosinophil counts per millimeter of epithelium in histamine-challenged animals that received 10 mg/kg (R)- rolipram were reduced by 79% compared to histamine-challenged controls (P < 0.01). The results indicate that (R)- rolipram inhibits the response to two distinct classes of mediator in this model of eosinophil infiltration, adding support to the contention that isozyme IV-selective cAMP phosphodiesterase inhibitors offer therapeutic potential for human asthma.
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Authors | S J Newsholme, L Schwartz |
Journal | Inflammation
(Inflammation)
Vol. 17
Issue 1
Pg. 25-31
(Feb 1993)
ISSN: 0360-3997 [Print] United States |
PMID | 8381769
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Isoenzymes
- Leukotrienes
- Pyrrolidinones
- Histamine
- 3',5'-Cyclic-AMP Phosphodiesterases
- Rolipram
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Topics |
- 3',5'-Cyclic-AMP Phosphodiesterases
(antagonists & inhibitors)
- Animals
- Asthma
(drug therapy)
- Conjunctiva
(drug effects)
- Conjunctivitis
(chemically induced, prevention & control)
- Eosinophilia
(chemically induced, prevention & control)
- Eosinophils
(drug effects)
- Guinea Pigs
- Histamine
(pharmacology, toxicity)
- Isoenzymes
(drug effects)
- Leukotrienes
(pharmacology, toxicity)
- Male
- Pyrrolidinones
(pharmacology)
- Rolipram
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