title: Effects of E-1020, a new cyclic AMP-specific phosphodiesterase inhibitor, on cyclic AMP and cytosolic free calcium of cultured vascular smooth muscle cells.
abstract: The purpose of this study is to clarify the pharmacological effects of E-1020 a new cAMP-specific phosphodiesterase (PDE) inhibitor, on cAMP or cytosolic free calcium (Ca) of cultured vascular smooth muscle cells (VSMC). VSMC were separated from the thoracic aorta of 2- to 3-month-old Wistar Kyoto rats (WKY). cAMP was measured by using the 125I-cAMP radioimmunoassay kit. The cytosolic free Ca of VSMC was measured by using the fluorescence Ca indicator, Fura-2/acetoxymethyl ester (Fura-2/AM). As a result, E-1020 increased the cAMP of VSMC in a dose-dependent manner, and about two fold increase in cAMP was observed by 10(-4) M E-1020. E-1020 decreased the cytosolic free concentration of Ca in a dose-dependent manner, and a significant decrease in cytosolic free Ca was observed by greater than 10(-6) M E-1020. These effects of E-1020 on cAMP and cytosolic free Ca were enhanced in the presence of low concentration (10(-8) M) of DL-noradrenaline. That is, a more prominent decrease in cytosolic free Ca than that of E-1020 alone was observed. Our results show that E-1020 decreases cytosolic free Ca of VSMC in parallel with increase in cAMP, and thereby suggest a potential vasodilating activity in vivo.
authors.affiliation: Department of Internal Medicine, Shimane Medical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohoka
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Morioka
authors.forename: S
authors.initials: S
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Yamori
authors.forename: K
authors.initials: K
authors.lastname: Moriyama
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C059498:olprinone; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine