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Am J Physiol Lung Cell Mol Physiol 284: L1045-L1054, 2003. First published January 31, 2003; doi:10.1152/ajplung.00054.2002
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Vol. 284, Issue 6, L1045-L1054, June 2003

ChTX induces oscillatory contraction in guinea pig trachea: role of cyclooxygenase-2 and PGE2

Yukihiro Yagi, Masayoshi Kuwahara, and Hirokazu Tsubone

Department of Comparative Pathophysiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan

We examined the possible role of cyclooxygenase (COX) in charybdotoxin (ChTX)-induced oscillatory contraction in guinea pig trachea. Involvement of prostaglandin E2 (PGE2) in ChTX-induced oscillatory contraction was also investigated. ChTX (100 nM) induced oscillatory contraction in guinea pig trachea. The mean oscillatory frequency induced by ChTX was 10.7 ± 0.8 counts/h. Maximum and minimum tensions within ChTX-induced oscillatory contractions were 68.4 ± 1.8 and 14.3 ± 1.7% compared with K+ (72.7 mM) contractions. ChTX-induced oscillatory contraction was completely inhibited by indomethacin, a nonselective COX inhibitor. Valeryl salicylate, a selective COX-1 inhibitor, did not significantly inhibit this contraction, whereas N-(2-cyclohexyloxy-4-nitro-phenyl)-methanesulfonamide, a selective COX-2 inhibitor, abolished this contraction. Exogenously applied arachidonic acid enhanced ChTX-induced oscillatory contraction. SC-51322, a selective PGE receptor subtype EP1 antagonist, significantly inhibited ChTX-induced oscillatory contraction. Exogenously applied PGE2 induced only a slight phasic contraction in guinea pig trachea, but PGE2 induced strong oscillatory contraction after pretreatment with indomethacin and ChTX. Moreover, ChTX time-dependently stimulated PGE2 generation. These results suggest that ChTX specifically activates COX-2 and stimulates PGE2 production and that ChTX-induced oscillatory contraction in guinea pig trachea is mediated by activation of EP1 receptor.

airway smooth muscle; calcium-activated potassium channel; prostaglandin E2; charybdotoxin


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[Abstract] [Full Text] [PDF]


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