Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by simvastatin leads to inhibition of both cell growth and Na+/H+ antiport activity. The effect of simvastatin on intracellular pH and Na+/H+ antiport activity was therefore studied on an adherent cell line, the SV40-virus-transformed MRC5 human fibroblast. 2. Simvastatin led to a dose-dependent decrease in intracellular pH, attributed to a reduction in Na+/H+ exchange, together with a rounding of cell shape. Mevalonate (1 mmol/l) prevented these effects of simvastatin, and when added after inhibition of the antiport by simvastatin, reversed these changes within 1-2h. 3. The phenomenon of mevalonate reversal of antiport inhibition by simvastatin was not sensitive to cycloheximide, indicating its post-translational nature. This was also consistent with the short period of incubation with mevalonate leading to reversal of antiport inhibition (1-2 h). These changes in intracellular pH regulation were not due to alterations in cell cholesterol content. 4. A variety of inhibitors of post-translational processes, such as N-linked glycosylation (tunicamycin), phosphorylation (staurosporine), isoprenylation (farnesol, limonene), and of pertussis-toxin-sensitive G-proteins or calmodulin (W7), had no effect on the reversal by mevalonate of simvastatin-induced changes in Na+/H+ antiport activity. 5. N-Ethylmaleimide (50 mumol/l for 5 min) prevented mevalonate reversing the effects of simvastatin, suggesting the importance of thiol groups in the phenomenon of reversal of the inhibition of Na+/H+ antiport activity by simvastatin. Furthermore, concurrent incubation of simvastatin-treated cells with dithiothreitol (1 mmol/l) and N-ethylmaleimide restored the ability of mevalonate to reverse the inhibitory effects of simvastatin on Na+H+ antiport activity.
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PMID:Simvastatin and intracellular pH regulation by the Na+/H+ antiport of SV40-virus-transformed human MRC5 fibroblasts. 839 20

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 (I(NSC)) in guinea pig cardiac ventricular myocytes. External LPC (3 to approximately 50 microM) induced I(NSC) in a dose-dependent manner with a lag. With fluvastatin (5 microM) in the external solution, LPC induced I(NSC), which was significantly smaller and with a longer lag compared with that in the absence of fluvastatin. With mevalonic acid (MVA) (100 microM) in the external solution, fluvastatin did not diminish LPC-induced I(NSC). Geranylgeranylpyrophosphate, an MVA metabolite, in the pipette solution prevented fluvastatin from diminishing LPC-induced I(NSC), 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 I(NSC). We conclude that LPC induces I(NSC) via a Gi/Go-coupled receptor and Rho-mediated pathway. The inhibitory effect of fluvastatin on LPC-induced I(NSC) provides a new insight into the signal transduction mechanism and may have important clinical implications.
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PMID:Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective cation current in Guinea pig ventricular myocytes. 1218 36