ELSEVIER zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA PI1 s0024-3205(97)00139-2 ure sciinre* vol. 60, No. m, pp. 175%1alk zyxwvutsrq 1997 zyxwvuts Copyr ight 0 1997 Ekvier Science Inc. Printed in the USA. All ri9* lrnrJ 0024-3205/97 sn.oa t .w POLYAMINE TRANSPORT SYSTEMS OF Leishmaniu donovani PROMASTIGOTES Mamta Kandpal and Babu L. Tekwani* Division of Biochemistry, Central Drug Research Institute, Lucknow- 001 (UP) INDIA (Received in final form February 10, 1997) summarv The following observations are conjointly indicative of the presence of distinct energy- dependent, saturable and multiple polyamine transport systems in Leishmania donovani promastigotes, the causative agent for visceral leishmaniasis. Spermidine was influxed with as much as seven times higher rate than putrescine, while both spermidine and putrescine transporters exhibited equally high affinity for the respective polyamine. N-Ethylmaleimide arrested the complete functionality of both the transporters which could be restored by reduced glutathione. Putrescine transporter did not recognize spermine but spermidine was recognized to some extent, while spermidine transporter significantly recognized spermine but putrescine was absolutely spared. A few aromatic diamines viz., diaminobiphenyl and the analogs as well as aliphatic diamines viz., cadaverine and agmatine were selectively recognized by the putrescine transporter only. L. donovani promastigotes grown in presence of a-difluoromethylomithine, an irreversible inhibitor of ornithine decarboxylase, registered marked upregulation of putrescine transport while spermidine transport was only marginally induced. PA transport systems provide the alternative pool of polyamines in L. donovani promastigotes in the absence of an adequate intracellular PA repertoire. Key Words: polyamine transport systems, zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIH Leishntmiu dmovuni, visceral leishmaniasis, putrescine, sptmnidine Polyamines (PAS) viz., putrescine (Put), spermidine (Spd) and spermine @pm) are polycationic biomolecules which are ubiquitous in occurrence and indispensable for normal cellular activities like growth, proliferation, differentiation and development (1). A definite role of PAS in the growth and proliferation of eukaryotic cells was shown by growing them in the presence of specific inhibitors of PA biosynthesis (2,3). Such studies on Leishmunia donovani , the causative agent of visceral leishmaniasis ( Indian Kala Azar), have revealed that a - difluoromethylomithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), was a potent inhibitor of leishmanial enzyme too (4). Even when 10 mh4 DFMO was present in the rich culture medium containing brain-heart infusion, the leishmania promastigotes after facing the initial mild shock, were able to survive with unaltered growth rates. However, when these cells were reseeded in a defined medium essentially free of PAS, containing the same concentration of DFMO, proliferation of promastigotes was completely arrested within 24 to 48 hours (4,5). DFMO was also found ineffective in vivo against L. donovani (6,7) Interruption with accumulation of PAS offers a potential target for chemotherapy of infections caused by *Corresponding author- Phone-91-522-225932: FAX- 91-522-22340s; Email-root%cdrilk@simetd.emet.in