POLYAMINE TRANSPORT IN MAMMALIAN-CELLS - AN UPDATE

The uptake and release of the natural polyamines putrescine, spermidin e and spermine by mammalian cells are integral parts of the systems th at regulate the intracellular concentrations of these biogenic amines according to needs. Although a general feature of all tissues, polyami ne uptake into intestinal mucosa cells is perhaps the most obvious pol yamine transport pathway of physiological and pathophysiological impor tance. Mutant cell lines lacking the ability to take up polyamines fro m the environment are capable of releasing polyamines. This indicates that uptake and release are functions of two different transport syste ms. The isolation of a transporter gene from a mammalian cell line is still lacking. Overaccumulation of polyamines is controlled by release and by a feedback regulation system that involves de novo synthesis o f antizyme, a sell known protein that also regulates the activity of o rnithine decarboxylase. Recent work has demonstrated that Ca2+-signall ing pathways are also involved. Although there is consensus about the importance of polyamine uptake inhibitors in the treatment of neoplast ic disorders, a practically useful uptake inhibitor is still missing. However, the attempts to target tumours, and to increase the selectivi ty of cytotoxic agents by combining them with the polyamine structure, are promising. New, less toxic and more selective anticancer drugs ca n be expected from this approach. Copyright (C) 1996 Elsevier Science Ltd