title: Butylidenephthalide blocks potassium channels and enhances basal tension in isolated guinea-pig trachea.
abstract: Butylidenephthalide (Bdph, 30~300 μM), a constituent of Ligusticum chuanxiong Hort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 μM), and its tension changes were isometrically recorded. Cromakalim (3 μM), an ATP-dependent K+ channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 μM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 μM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 μM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 μM) and 4-aminopiridine (4-AP, 5 mM), a blocker of K v 1 family of K+ channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of K v 1 family of K+ channels, to enhance the baseline tension of guinea-pig trachea.
authors.affiliation: Department of Otolaryngology, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Hsin-Te
authors.initials: HT
authors.lastname: Hsu
authors.affiliation: School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taiwan.
authors.forename: You-Lan
authors.initials: YL
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 110, Taiwan ; Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Wun-Chang
authors.identifier: 0000-0002-1823-9824
authors.initials: WC
authors.lastname: Ko
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004336:Drug Antagonism; D006168:Guinea Pigs; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010796:Phthalic Anhydrides; D015221:Potassium Channels; D014700:Verapamil; D009543:Nifedipine; C026105:butylidenephthalide