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Notes: 1. The aim of the present study was to investigate the possibility that, in the two cell lines examined, alterations in cell growth caused by lipophilic quaternary ions may involve KATP channels. We examined the effect of tetraphenylphosphonium (TPP), tetraphenylboron (TPB), rhodamine 123, dequalinium chloride (DECA) and the non-quaternary ion cisplatin on the proliferation of L1210 mouse leukaemia cells and rat smooth muscle cells in vitro. The KATP channel opener levcromakalim (LKM) and the Katp channel antagonist glibenclamide were also tested.2. From growth-inhibition studies, the rank order of potency (based on pIC50 values) using L1210 leukaemia cells was: DECA (6.61) 〉 cisplatin (6.09) = rhodamine 123 (6.01) 〉 TPP (5.61) 〉 TPB (4.25). Levcromakalim and glibenclamide were found to be inactive at the maximum concentrations used (100 μmol/L). A different rank order of potency was obtained in rat aortic smooth muscle cells: cisplatin (6.33) 〉 DECA (5.67) 〉 TPP (4.96) 〉 rhodamine 123 (4.1). Tetraphenylboron (30μmol/L), LKM (100 μmol/L) and glibenclamide (100 μmol/L) were found to be inactive.3. When the negatively charged TPB (30 μmol/L) was combined with some of the active agents, the potency of the active agents was increased. Thus, in L1210 cells, rhodamine 123, DECA and TPP were all more potent at inhibiting cell growth in the presence of TPB. Tetraphenylboron had no effect on cisplatin in this cell line. In rat smooth muscle cells, TPB (30 μ mol/L) potentiated the effect of rhodamine 123 but had no effect on the actions of cisplatin, DECA or TPP.4. In functional studies, rhodamine 123 was a weak antagonist of the vasorelaxant responses to the KATP channel opener LKM in the porcine right circumflex artery in vitro. The pKB value obtained for rhodamine 123 at 100 μmol/L was 4.95. Dequalinium chloride was inactive.5. We found no correlation between the actions of the compounds tested to antagonize KATP channels and their ability to inhibit cell proliferation. In addition, compounds known to regulate KATP channel activity failed to influence proliferative rates. These results suggest that KATP channels are not involved in the antiproliferative action of TPP and other quaternary ions in the two cell lines studied.