title: Pharmacological characteristics of MJ-451, a new benzopyran- derived ATP-sensitive potassium channel opener, in guinea pig isolated trachea.
abstract: In this study, we determined the pharmacological activities of MJ-451 (6-cyano-3S,4R-dihydro-2, 2-dimethyl-2H-3-hydroxy-4-[2-oxo-5S-1-hydroxmethyl)-1-pyrrolidinyl ]-1 -benzopyran) in guinea pig isolated trachea and compared its effects with those of cromakalim. MJ-451 (0.1-10 micromol/l) and cromakalim (0.01-1 micromol/l) produced concentration-dependent relaxation of guinea pig isolated trachea precontracted with carbachol (0.5 micromol/l) or histamine (1 micromol/l). MJ-451 (0.03-30 micromol/l), as well as cromakalim (0.03-30 micromol/l), caused a complete and concentration-dependent relaxation of guinea pig isolated trachea precontracted with 20 mmol/l KCl, but did not inhibit the spasmogenic effect of 80 mmol/l KCl. However, theophylline (30-3,000 micromol/l) caused a complete and concentration-dependent relaxation of guinea pig isolated trachea precontracted with either 20 or 80 mmol/l KCl. Propranolol (0.1 micromol/l) markedly antagonized the relaxant action of isoprenaline, but not that of MJ-451 in carbachol-contracted isolated trachea. 8-(p)-sulfophenyltheophylline (150 micromol/l), a selective P1 purinoceptor antagonist, had no effect against the tracheal relaxation induced by MJ-451, but markedly depressed the concentration-response curve of 5'-N-ethylcarboxamidoadenosine. Charybdotoxin (10 micromol/l), a large-conductance Ca2+-activated K+ channel blocker, failed to modify the relaxant activity of MJ-451 in carbachol-contracted isolated trachea. The ATP-sensitive K+ channel blocker, glibenclamide (0.1, 1 and 10 micromol/l) concentration-dependently antagonized the relaxant activity of MJ-451 in carbachol-contracted isolated trachea. It is concluded that MJ-451 is a selective ATP-sensitive K+ channel opener in the tracheal smooth muscle of the guinea pig.
authors.affiliation: Department of Medical Technology, Taipei Medical College, National Taiwan University, Taipei, Taiwan.
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Sheu
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Yen
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D014132:Trachea
chemical_list: D001578:Benzopyrans; D010276:Parasympatholytics; D010277:Parasympathomimetics; D015221:Potassium Channels; D011760:Pyrrolidinones; D019806:Cromakalim; C116250:MJ 451; D011189:Potassium Chloride; D006632:Histamine; D002217:Carbachol