ChTX induces oscillatory contraction in guinea pig trachea: role of cyclooxygenase-2 and PGE2.
We examined the possible role of cyclooxygenase (COX) in charybdotoxin (ChTX)-induced oscillatory contraction in guinea pig trachea. Involvement of prostaglandin E(2) (PGE(2)) 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 EP(1) antagonist, significantly inhibited ChTX-induced oscillatory contraction. Exogenously applied PGE(2) induced only a slight phasic contraction in guinea pig trachea, but PGE(2) induced strong oscillatory contraction after pretreatment with indomethacin and ChTX. Moreover, ChTX time-dependently stimulated PGE(2) generation. These results suggest that ChTX specifically activates COX-2 and stimulates PGE(2) production and that ChTX-induced oscillatory contraction in guinea pig trachea is mediated by activation of EP(1) receptor.
Yagi
Yukihiro
Y
Department of Comparative Pathophysiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
Kuwahara
Masayoshi
M
Tsubone
Hirokazu
H
D000818:Animals; D018999:Charybdotoxin / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006168:Guinea Pigs; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010507:Periodicity; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors; D058306:Receptors, Prostaglandin E, EP1 Subtype; D019789:Tetraethylammonium / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D007527:Isoenzymes; D008565:Membrane Proteins; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D018999:Charybdotoxin; D019789:Tetraethylammonium; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone