RT Journal Article SR Electronic T1 Inhibitory Effect of Fluvastatin on Lysophosphatidylcholine-Induced Nonselective Cation Current in Guinea Pig Ventricular Myocytes JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 602 OP 607 DO 10.1124/mol.62.3.602 VO 62 IS 3 A1 Libing Li A1 Isao Matsuoka A1 Yuichi Suzuki A1 Yasuhide Watanabe A1 Toshiyuki Ishibashi A1 Keiko Yokoyama A1 Yukio Maruyama A1 Junko Kimura YR 2002 UL http://molpharm.aspetjournals.org/content/62/3/602.abstract AB Using the whole-cell voltage-clamp method, we investigated the effect of fluvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on lysophosphatidylcholine (LPC)-induced nonselective cation current (INSC) in guinea pig cardiac ventricular myocytes. External LPC (3∼50 μM) induced INSC in a dose-dependent manner with a lag. With fluvastatin (5 μM) in the external solution, LPC induced INSC, which was significantly smaller and with a longer lag compared with that in the absence of fluvastatin. With mevalonic acid (MVA) (100 μM) in the external solution, fluvastatin did not diminish LPC-induced INSC. Geranylgeranylpyrophosphate, an MVA metabolite, in the pipette solution prevented fluvastatin from diminishing LPC-induced INSC, suggesting that isoprenylated signaling molecules, such as the small G-protein Rho, might be involved in the LPC effect. Botulinum toxin C3, Rho-kinase inhibitor (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide, 2 HCl (Y-27632), or pertussis toxin in the pipette solution suppressed LPC-induced INSC. We conclude that LPC induces INSC via a Gi/Go-coupled receptor and Rho-mediated pathway. The inhibitory effect of fluvastatin on LPC-induced INSCprovides a new insight into the signal transduction mechanism and may have important clinical implications.