Alkaloid transport

This idea that indole alkaloids transport across tonoplast could be mediated by a highly specific energy dependent carrier was proposed and... 

Majerus and Pareilleux (775) observed that a sudden drop in pH from 6.0 to 5.0 resulted in enhanced excretion of tryptamine and ajmalicine in a continuous culture of immobilized C. roseus cells. From the literature it becomes clear that the pH of the culture influences alkaloid transport between cells and medium. Whether the external pH also affects alkaloid biosynthesis is still a matter of investigation. 

At present, only a few membrane compartments, transporters and channels are known to have a defined role in alkaloid transport and compartmentation. One major challenge for research is the high individuality in the cellular organization that rests on the species-specific localization of biosynthetic enzymes and the opportunistic use of transporters, metabolite pools, storage sites and accumulation mechanisms even between taxonomically related genera. 

There is little doubt that the few examples of alkaloid transporters known today will be greatly expanded in the next future as the perfection of molecular and cellular techniques should allow to characterize suspected transport mechanism and proteins and that hitherto escaped the experimental access. Candidates will be found not only among the steps of intracellular accumulation and transport as postulated above, but also within the long known inter-organ transfers, e.g. of nicotine from the root to leave vacuoles in Nicotiana (Hashimoto and Yamada, 1994) or of senecionine-N-oxide from the roots to vacuoles of inflorescences in Senecio (Hartmann, 1999). 

Shitan N, Bazin I, Dan K, et al. (2003) Involvement of CjMDRl, a plant multidrug-resistance-type ATP-binding cassette protein, in alkaloid transport in Coptis japonica. Proc Natl Acad Sci USA 100 751-756... 

It is interesting to note that the intracellular transport of some alkaloids in plants, such as berberine, also appears to be catalysed hy plant ABC transporters (69,70,359). It was shown that many alkaloids are transported by alkaloid/H antiporters (71). At that time, ABC transporters were unknown. Since these antiporters were ATP-dependent, it might be worthwhile to revisit alkaloid transport mechanisms in plants (359). 

After determination of the seasonal variation in alkaloidal content of the leaves, stems and roots of belladonna and the production of evidence that there is a considerable movement of alkaloid upwards from root to leaves and a small transport in the opposite direction, Cromwell found that of a laige number of amines injected, with or without glucose, into... 

Vinca alkaloids (vincristine, vinblastine, vindesine) are derived from the periwinkle plant (Vinca rosea), they bind to tubulin and inhibit its polymerization into microtubules and spindle formation, thus producing metaphase arrest. They are cell cycle specific and interfere also with other cellular activities that involve microtubules, such as leukocyte phagocytosis, chemotaxis, and axonal transport in neurons. Vincristine is mainly neurotoxic and mildly hematotoxic, vinblastine is myelosuppressive with veiy low neurotoxicity whereas vindesine has both, moderate myelotoxicity and neurotoxicity. 

Vinca alkaloids are derived from the Madagascar periwinkle plant, Catharanthus roseus. The main alkaloids are vincristine, vinblastine and vindesine. Vinca alkaloids are cell-cycle-specific agents and block cells in mitosis. This cellular activity is due to their ability to bind specifically to tubulin and to block the ability of the protein to polymerize into microtubules. This prevents spindle formation in mitosing cells and causes arrest at metaphase. Vinca alkaloids also inhibit other cellular activities that involve microtubules, such as leukocyte phagocytosis and chemotaxis as well as axonal transport in neurons. Side effects of the vinca alkaloids such as their neurotoxicity may be due to disruption of these functions. 

Dopamine depleting agents. Reserpine, a natural alkaloid that blocks vesicular transport of monoamines, depletes stored monoamines, including DA. DA depletion is associated with the emergence of parkinsonism. This effect of reserpine was among the first clues that PD is the result of DA deficiency (see above). Generally, the parkinsonism resulting from reserpine is reversible. 

The coca leaf is either consumed by the natives of South America or exported to other countries for consumption. Another use of the coca leaf is in the extraction of cocaine either for illegitimate or legitimate use. The majority of the legal and/or clandestine cocaine factories are in South America due to the cost and bulk of transporting the whole leaf. In 1961, Bolivia produced an annual crop of from 12,000 to 18,000 tons of leaves although only half reached the legal market. The alkaloid cocaine is extracted from the coca leaf in basically three different chemical procedures. These procedures are used both in licit and illicit labs in the production of cocaine. 

Chewing leaves of the khat shrub is practiced in parts of East Africa and the Arabian peninsula (Kalix 1988 Widler et al. 1994). Some estimate daily use at 5 million portions. Use in the West is less common, but has increased somewhat. More common in the United States has been use of the synthetic drug methcathinone (or "cat"), which is derived from khat alkaloids. Only the fresh khat leaves are pharmacologically active, so for some time use was limited to local areas that grew the plant. However, with air transportation, use has spread with emigrants in Europe and the United States. Because of its pharmacological similarities to amphetamine and its addictive properties, khat has been listed on Schedule I of the United Nations Convention on Psychotropic Substances. 

Lavie, Y., Harel-Orbital, T., Gaffield, W. and Liscovitch, M. (2001). Inhibitory effect of steroidal alkaloids on drug transport and multidrug resistance in human breast cancer cells. Anticancer Res., 21, 1189-1194. 

Otani M, Shitan N, Sakai K, Martinoia E, Sato F, Yazaki K. (2005) Characterization of vacuolar transport of the endogenous alkaloid berberine in Coptis japonica. Plant Physiol 138 1939-1946. 

Drug resistance in vitro and probably in vivo results both from inhibition of influx of the vinca alkaloids and, perhaps more frequently, from promotion of their efflux out of cells (34,35). Until relatively recently, the former mechanism was thought to predominate, and, indeed, certain acquired drug-resistant states are clearly associated with the loss of membrane proteins which can be shown to bind and transport agents into cells (34). However, other resistant states have been shown to be associated with the acquisition of membrane transport proteins which remove toxins (and, therefore, chemotherapeutic agents) both from normal and malignant cells. 

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