title: Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells.
abstract: In this study, we investigated the effects of a combination of Ginkgo biloba extracts (GBE) and phosphodiesterase type 5 (PDE-5) inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1×10⁻⁵ mol l⁻¹ norepinephrine, GBE (0.01-1 mg ml⁻¹) and mirodenafil (0.01-100 nmol l⁻¹) were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavernosum was relaxed in response to GBE in a dose-dependent manner (from 0.64%±8.35% at 0.01 mg ml⁻¹ to 52.28% ± 11.42% at 1 mg ml⁻¹). After pre-treatment with 0.03 mg ml⁻¹ of GBE, the relaxant effects of mirodenafil were increased at all concentrations. After tetraethylammonium (TEA) (1 mmol l⁻¹) administration, the increased effects were inhibited (P<0.01). Extracellular administration of GBE increased the whole-cell K(+) outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by 1 mmol l⁻¹ TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K(+) flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation.
authors.affiliation: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors.forename: Jung Jun
authors.initials: JJ
authors.lastname: Kim
authors.forename: Deok Hyun
authors.initials: DH
authors.lastname: Han
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lim
authors.forename: Tae Hun
authors.initials: TH
authors.lastname: Kim
authors.forename: Mee Ree
authors.initials: MR
authors.lastname: Chae
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Chung
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Kam
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000818:Animals; D020441:Ginkgo biloba / Q000737:chemistry*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010413:Penis / Q000187:drug effects* / Q000503:physiopathology; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010936:Plant Extracts; D015221:Potassium Channels; D011744:Pyrimidinones; D013449:Sulfonamides; C528396:mirodenafil