This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration-dependently. P 1060, RP 49356 and BRL 38227 suppressed the maximal responses to bethanechol and shifted the concentration-response curves of bethanechol-induced contraction to the right. RP 49356 and BRL 38227 reduced the contraction by low (20 mM) concentration of potassium. P 1060, however, diminished the high (80 mM) and low (20 mM) concentration of potassium-induced contraction. Glibenclamide, an inhibitor of ATP-dependent potassium channel, antagonized the suppressive action of P 1060, RP 49356 and BRL 38227 on the basal tone. Apamin or procaine did not antagonize it significantly. Based on these results, it is suggested that the relaxation of detrusor muscle strip caused by P 1060, RP 49356 and BRL 38227 may predominantly involve opening of the same potassium channel, i.e., the ATP-dependent potassium channel.
Animals ; Benzopyrans/*pharmacology ; Cromakalim ; Guanidines/*pharmacology ; Muscle Contraction/drug effects ; Muscle, Smooth/*drug effects ; Picolines/*pharmacology ; Potassium Channels/*drug effects ; Pyrans/*pharmacology ; Pyrroles/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder/*drug effects/physiology

OBJECTIVE: To investigate the feasibility of a novel molecular probe of Zn-DPA-PSS794 to monitor the efficiency of doxorubicin to ovarian cancer and compare with Cy5.5-annexin V. METHODS: Efficiency of doxorubicin to OVCAR-8 cells in vitro was measured by MTT assay and flow cytometry. The in vivo studies were performed on an OVCAR-8 xenograft tumor model. Mice were divided into a control group and a treatment group. Each group was divided into 2 subgroups, DPA and annexin V. In the treatment group, the mice were treated with doxorubicin for 2 doses. All mice were performed optical imaging by Zn-DPA-PSS794 or Cy5.5-annexin V, respectively and then sacrificed. The tumor was separated and stained by HE. The expression of caspase-3 protein was measured by Western blot. RESULTS: The IC50 of doxorubicin to OVCAR-8 was 6 μmol/L. The percentage of apoptosis and dead cells was 35% after doxorubicin treatment. In the optical image, photons accumulated in the tumor either by Zn-DPA-PSS794 or Cy 5.5-annexin V in the treatment group. That was negative in the control group. The fluorescence intensity had significant difference between the 2 groups(P<0.001). The nuclei were big and stained with deep color after the cells were stained with HE. The caspase-3 expression was high in the treatment group, while it was low in the control group. CONCLUSION Zn-DPA-PSS794 as a probe used by optical imaging can monitor the efficiency of doxorubicin to OVCAR-8 xenograft tumor, which is similar to Cy5.5-annexin V.
Animals ; Apoptosis ; drug effects ; Carbocyanines ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Female ; Fluorescent Dyes ; Humans ; Infrared Rays ; Mice ; Mice, Nude ; Molecular Imaging ; Organometallic Compounds ; Ovarian Neoplasms ; pathology ; Picolines ; Spectroscopy, Near-Infrared ; methods