K-ATP channel blocking actions of quaternary ions play no role in their antiproliferative action on mouse leukaemia and rat vascular smooth muscle cells in vitro

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 lipophil ic quaternary ions may involve K-ATP channels, We examined the effect of te traphenylphosphonium (TPP), tetraphenylboron (TPB), rhodamine 123, dequalin iun chloride (DECA) and the non-quaternary ion cisplatin on the proliferati on of 1,1210 mouse leukaemia cells and rat smooth muscle cells in vitro, Th e K-ATP channel opener levcromakalim (LKM) and the K-ATP channel antagonist glibenclamide were also tested. 2. From growth-inhibition studies, the rank order of potency (based on pIC( 50) values) using L1210 leukaemia cells was: DECA (6.61) > cisplatin (6.09) = rhodamine 123 (6.01) > TPP (5.61) > TPB (4.25). Levcromakalim and gliben clamide were found to be inactive at the maximum concentrations used (100 m u mol/L). A different rank order of potency was obtained in rat aortic smoo th muscle cells: cisplatin (6.33) > DECA (5.67) > TPP (4.96) > rhodamine 12 3 (4.1). Tetrapbenylboron (30 mu mol/L), LKM (100 mu mol/L) and glibenclami de (100 mu mol/L) were found to be inactive. 3. When the negatively charged TPB (30 mu mol/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 inhibitin g cell. growth in the presence of TPB, Tetraphenylboron had no effect on ci splatin in this cell line, In rat smooth muscle cells, TPB (30 mu mol/L) po tentiated the effect of rhodamine 123 but had no effect on the actions of c isplatin, DECA or TPP. 4. In functional studies, rhodamine 123 was a weak antagonist of the vasore laxant responses to the K-ATP channel opener LKM in the porcine right circu mflex artery in vitro, The pK(B) value obtained for rhodamine 123 at 100 mu mol/L was 4.95. Dequalinium chloride was inactive. 5. We found no correlation between the actions of the compounds tested to a ntagonize KATP channels and their ability to inhibit cell proliferation, In addition, compounds known to regulate KATP channel activity failed to infl uence proliferative rates. These results suggest that K-ATP channels are no t involved in the antiproliferative action of TPP and other quaternary ions in the two cell lines studied.