title: Effects of vesnarinone (OPC-8212) on Ca(2+)-activated K channels and cytosolic Ca2+ in cultured smooth muscle cells from porcine coronary artery.
abstract: Vesnarinone is a new, non vasodilating cardiotonic agent. This study compared the effects of vesnarinone and amrinone, a phosphodiesterase (PDE) inhibitors with vasodilating actions, on cultured smooth muscle cells from the porcine coronary artery. Application of vesnarinone (10(-4) M) or amrinone (10(-4) M) to the bath solution in cell-attached patches activated the KCa channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytosolic side had no direct effect on KCa channel activities in inside-out patches. Activation of the KCa channel was suppressed when the intracellular production of cAMP was suppressed by preincubation with carbachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in the K(+)-depolarized smooth muscle cells (K+ = 70 mM). These results suggest that vesnarinone exerts an additional effect on [Ca2+]i that is independent of PDE inhibition. The difference in the effects on [Ca2+]i in vascular smooth muscle cells may explain in part the differing actions of these agents on vascular relaxation.
authors.affiliation: School of Medical Science, University of Tokushima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: T
authors.initials: T
authors.lastname: Wakatsuki
authors.forename: M
authors.initials: M
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Shono
mesh_terms: D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D015221:Potassium Channels; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone; D002217:Carbachol; D000242:Cyclic AMP; D000676:Amrinone; D002118:Calcium