Role of cyclooxygenase isoforms and nitric-oxide synthase in the modulation of tracheal motor responsiveness in normal and antigen-sensitized Guinea pigs
| Autor: | Paola Nieri, Maria Cristina Breschi, Corrado Blandizzi, Chiara Ippolito, Nunzia Bernardini, Cinzia Martinelli, Mario Del Tacca, Rosamiria Greco |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Ovalbumin Guinea Pigs Prostacyclin Dinoprostone Guinea pig Contractility chemistry.chemical_compound Internal medicine medicine Animals Prostaglandin E2 Sensitization Pharmacology COX-1 COX-2 trachea allergy guinea-pig nitric oxide synthase biology Epoprostenol Immunohistochemistry Nitric oxide synthase Trachea Endocrinology medicine.anatomical_structure NG-Nitroarginine Methyl Ester chemistry Cyclooxygenase 2 Immunology biology.protein Cyclooxygenase 1 Molecular Medicine Cyclooxygenase Nitric Oxide Synthase Histamine medicine.drug Muscle Contraction |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 319(2) |
| ISSN: | 0022-3565 |
| Popis: | The effects of selective cyclooxygenase (COX) isoform (COX-1, COX-2) inhibition, alone or in combination with nitric-oxide synthase (NOS) blockade, on in vitro tracheal muscle responsiveness to histamine were investigated in healthy and ovalbumin (OVA)-sensitized guinea pigs. Immunohistochemistry showed that COX-1 and COX-2 are constitutively present in normal guinea pig trachea, particularly in the epithelial layer, and that COX-2 expression is enhanced in OVA-sensitized animals both in epithelial and subepithelial tissues. In normal guinea pigs, SC-560 \[5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole\] (COX-1 inhibitor) or DFU \[5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5 H )-furanone\] (COX-2 inhibitor) significantly increased the contractile response to histamine, these effects being not additive. NOS inhibition by l- N G-nitro-arginine methyl ester (l-NAME) did not affect histamine-induced contraction but reversed the increase caused by COX-1 blockade while not modifying the enhancement associated with COX-2 inhibition. In guinea pigs subjected to OVA sensitization and challenge, COX-2, but not COX-1, inhibition enhanced the motor responses to histamine without any influence by l-NAME. In normal, but not in sensitized animals, the removal of epithelial layer from tracheal preparations abolished the enhancing action of DFU on histamine-mediated contraction. A COX-2-dependent release of prostacyclin (PGI2), but not prostaglandin E2, was observed in tracheal tissues from normal and OVA-sensitized guinea pigs. In conclusion, both COX-1 and COX-2 are constitutive in guinea pig trachea, and COX-2 expression is enhanced by OVA sensitization; in normal animals, epithelial COX-2 exerts a PGI2-dependent inhibitory control on tracheal contractility, and this isoform is subjected to upstream regulation by epithelial COX-1 and NOS through a complex interplay; and following antigen sensitization, the inhibitory control on tracheal contractility is maintained by COX-2 induced at subepithelial cell sites. |
| Databáze: | OpenAIRE |
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