Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways

Ricciardolo, F. L., Steinhoff, M., Amadesi, S., Guerrini, R., Tognetto, M., Trevisani, M., Creminon, C., Bertrand, C., Bunnett, N. W., Fabbri, L. M., Salvadori, S. and Geppetti, P. (2000) Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways. American Journal of Respiratory and Critical Care Medicine, 161 (5). pp. 1672-1680. ISSN 1535-4970 doi: 10.1164/ajrccm.161.5.9907133

Abstract/Summary

The protease activated receptor-2 (PAR-2) belongs to a family of G-protein-coupled receptors that are activated by proteolysis. Trypsin cleaves PAR-2, exposing an N-terminal tethered ligand (SLIGRL) that activates the receptor. Messenger RNA (mRNA) for PAR-2 was found in guinea pig airway tissue by reverse transcription-polymerase chain reaction, and PAR-2 was found by immunohistochemistry in airway epithelial and smooth-muscle cells. In anesthetized guinea pigs, trypsin and SLIGRL-NH(2) (given intratracheally or intravenously) caused a bronchoconstriction that was inhibited by the combination of tachykinin-NK(1) and -NK(2) receptor antagonists and was potentiated by inhibition of nitric oxide synthase (NOS). Trypsin and SLIGRL-NH(2) relaxed isolated trachea and main bronchi, and contracted intrapulmonary bronchi. Relaxation of main bronchi was abolished or reversed to contraction by removal of epithelium, administration of indomethacin, and NOS inhibition. PAR-1, PAR-3, and PAR-4 were not involved in the bronchomotor action of either trypsin or SLIGRL-NH(2), because ligands of these receptors were inactive either in vitro or in vivo, and because thrombin (a PAR-1 and PAR-3 agonist) did not show cross-desensitization with PAR-2 agonists in vivo. Thus, we have localized PAR-2 to the guinea-pig airways, and have shown that activation of PAR-2 causes multiple motor effects in these airways, including in vivo bronchoconstriction, which is in part mediated by a neural mechanism.

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Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/35824
Item Type	Article
Refereed	Yes
Divisions	No Reading authors. Back catalogue items Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
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Publisher	American Thoracic Society
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