The effect of verapamil, a calcium antagonist, on the serum-dependent regulation of uridine uptake by cells in culture.
The stimulation of uridine uptake is one of the early events that occur when quiescent cells are stimulated to grow by adding fresh serum. Serum depletion of cells in their exponential phase of growth results in a decrease of uridine uptake rate, a process which is complete before a significant reduction in DNA synthesis is observed. Elevation of extracellular potassium can stimulate the role of serum as an activator of uridine uptake, and can prevent the inhibition of uptake that results from serum depletion. Verapamil, a known antagonist of calcium movement across biological membranes, inhibits uridine uptake. This inhibition is much stronger in serum- or KCl-activated cells than in serum-depleted or quiescent cells. Verapamil can partially prevent the serum-dependent stimulation of uridine uptake. The effect of Verapamil does not depend on the presence of calcium in the extra-cellular medium. Verapamil may interfere with serum-dependent redistribution of Ca2+ within the cells, and thus uncouple the initial event of binding of serum growth factors to membrane receptors, from the subsequent intracellular response-regulation of uridine uptake rates.
D000818:Animals; D001769:Blood; D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D008647:Mesocricetus; D014529:Uridine / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology*
D015636:Magnesium Chloride; D014700:Verapamil; D008274:Magnesium; D002122:Calcium Chloride; D014529:Uridine