Role of cyclooxygenase isoforms and nitric-oxide synthase in the modulation of tracheal motor responsiveness in normal and antigen-sensitized Guinea pigs.

Content Provider	Semantic Scholar
Author	Nieri, Paola Martinelli, Cinzia Blandizzi, C. Bernardini, Nunzia Greco, Rosamiria Ippolito, Chiara Tacca, Mario Del Breschi, Maria Cristina
Copyright Year	2006
Abstract	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(5H)-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 (PGI(2)), but not prostaglandin E(2), 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 PGI(2)-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.
Starting Page	699
Ending Page	717
Page Count	19
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://jpet.aspetjournals.org/content/jpet/319/2/648.full.pdf
Alternate Webpage(s)	http://jpet.aspetjournals.org/content/jpet/early/2006/08/22/jpet.106.102475.full.pdf
PubMed reference number	16926267v1
Volume Number	319
Issue Number	2
Journal	The Journal of pharmacology and experimental therapeutics
Language	English
Access Restriction	Open
Subject Keyword	Alprostadil Arginine Body tissue Cavia porcellus Cyclooxygenase 2 Inhibitors Epoprostenol Esters Histamine Inhibitory Nerve Control NG-Nitroarginine Methyl Ester Nitric Oxide Synthase Ovalbumin PTGS1 protein, human Prostaglandin-Endoperoxide Synthase Protein Isoforms Sensitization (observable entity) Trachea
Content Type	Text
Resource Type	Article