ABSTRACT
The single channel current of intermediate conductance Ca2 +-activated K+ channel (IK channel) was measured in mouse urinary bladder myocytes (MBM), and the molecular basis of the channel was suggested to be the SK4 subtype by RT-PCR. Among Ca2+-activated K+ channel subtypes (SK2, SK3, SK4 and BK), the mRNAs of SK4 and BK were predominantly expressed in MBM. IK channel currents recorded from MBM showed: 38.7 pS slope conductance under symmetrical 140 mM K+ conditions, Ca2+-dependent activation, and blockade by charybdotoxin and econazole. These results strongly suggest that SK4 encodes IK channels in MBM.
Subject(s)
Muscle, Smooth/metabolism , Potassium Channels, Calcium-Activated , Potassium Channels/metabolism , Urinary Bladder/metabolism , Animals , Calcium/metabolism , Electrophysiology , In Vitro Techniques , Intermediate-Conductance Calcium-Activated Potassium Channels , Mice , Muscle, Smooth/physiology , Potassium Channels/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tissue Distribution , Urinary Bladder/physiologyABSTRACT
Effects of a new antiulcer drug, MCI-727, on gastric and duodenal lesions, gastric secretion and gastric motility were studied in comparison with cimetidine and teprenone. MCI-727 dose-dependently (3-100 mg/kg, p.o. or i.d.) inhibited the development of acute gastric or duodenal lesions such as pyrolus ligation-, water-immersion stress-, indomethacin-, HCl-, HCl-ethanol-induced gastric lesions and cysteamine-induced duodenal lesions in rats and histamine-induced duodenal lesions in guinea pigs. These antiulcer effects exceeded those of cimetidine or teprenone. Repeated administration of MCI-727 (0.3-3 mg/kg/day, p.o., for 10 days) significantly promoted the spontaneous healing of acetic acid-induced chronic gastric ulcers. Concerning gastric acid secretion, MCI-727 selectively inhibited tetragastrin-stimulated acid secretion without effecting basal acid secretion and acid secretion by other stimuli. Cimetidine and teprenone inhibited acid secretion in several cases. MCI-727 and teprenone had inhibitory effects on gastric motility, although cimetidine had no effect. These results suggest that MCI-727 has a wide spectrum of antiulcer activity, and its mode of antiulcer action is different from that of cimetidine or teprenone.
