Alkaloids uptake

Deus-Neumann, B. and Zenk, M.H. (1984) A highly selective alkaloid uptake system in vacuoles of higher plants. Planta, 162,250-60. 

Renaudin 84) studied the influence of pH on the uptake of indole alkaloids by C. roseus cells. He found that alkaloid uptake was influenced by both the intra- and extracelluar pH as well as the pAa of the alkaloid under study. From these results the conclusion was drawn that alkaloid uptake was caused by an ion-trap mechanism. Recent studies by Blom et al. 80,81) showed that the accumulation of ajmalicine in vacuoles of C. roseus is due to an ion-trap mechanism. In the vacuole ajmaUcine is converted to serpentine by basic peroxidases. Serpentine does not pass the tonoplast and is thus trapped in this way. No active transport of the alkaloids, as had been previously reported 74,75), could be detected. Pareilleux and Vinas 615) also attributed the changing ratio between intra-and extracellular concentrations of serpentine and ajmalicine in a batch culture of C. roseus grown in a 3.5-liter stirred tank reactor to a changing culture pH. 

Hantak MM, Grant T, Reinsch S, Mcginnity D, Loring M, ToyookaN, et al. Dietary Alkaloid Sequestration in a poison frog and experimental test of alkaloid uptake in Melanophryniscus stelzneri (Bufonidae). J Chem Ecol 2013 39(ll-12) 1400-6. 

Adler LS (2000) Alkaloid uptake increases fltness in a hemiparasitic plant via reduced herbivory and increased pollination. Am Nat 56 92-99... 

This type of action is found in kanna, or Sceletium expansum and Sceletium tortuosum (Aizoaceae), which have been used by South African shamans from prehistoric times to enhance animal spirits, sparkle the eyes, and to stimulate gaiety. The active constituent of kanna is a serotonin-like alkaloid called mesembrine, which is a potent serotonin re-uptake inhibitor—hence, some potential for the treatment of anxiety and depression however, careful clinical trials must be performed. 

Holz, K.W. and Coyle, J.T., The effects of various salts, temperature and the alkaloids veratridine and batrachotoxin on the uptake of pH]-dopamine into synatosomes from rat striatum, Mol. Pharmacol., 10, 746, 1974. 

The cause of the cell cycle specificity of the bisindole alkaloids may be associated with the ability of these compounds to interact with the protein tubulin and thereby inhibit the polymerization (and depolymerization) of microtubules (16,17). In this respect the cellular pharmacology of vinca alkaloids is similar to that of other cytotoxic natural products such as colchicine or podophyllotoxin. On closer inspection, however, Wilson determined that the specific binding site on tubulin occupied by vinblastine or vincristine is chemically distinct from the site occupied by the other natural products (18). Subsequent experiments have determined that the maytansinoids, a class of ansa-macrocycles structurally distinct from the bisindoles, may bind to tubulin at an adjacent (or overlapping) site (19). A partial correlation of the antimitotic activity of these compounds with their tubulin binding properties has been made, but discrepancies in cellular uptake probably preclude any quantitative relationship of these effects (20). 

Resistance to vinca alkaloids has been correlated with a decreased rate of drug uptake or an increased drug efflux from these tumor cells. Cross-resistance usually occurs with anthracycUnes, dactinomycin, and podophyllotoxins. 

Mechanism of Action An ergot alkaloid that centrally acts and decreases vascular tone, slows heart rate. Peripheral action blocks alpha-adrenergic receptors. Therapeutic Effect Improved Oj uptake and improves cerebral metabolism. Pharmacohinetics Rapidly, incompletely absorbed from GI tract. Metabolized in liver. Eliminated primarily in feces. Half-life 2-5 hr. 

Mecfianism of Action A cinchona alkaloid that relaxes skeletal muscle by increasing the refractory period, decreasing excitability of motor end plates (curare-like), and affecting distribution of calcium with muscle fiber. Antimalaria Depresses oxygen uptake, carbohydrate metabolism, elevates pH in intracellular organelles of parasites. Therapeutic Effect Relaxes skeletal muscle produces parasite death. Pharmacokinetics Rapidly absorbed mainly from upper small intestine. Protein binding 70%-95%. Metabolized in liver. Excreted in feces, saliva, and urine. Half-life 8-14 hr (adults), 6-12 hr (children). 

Wink, M. L. D. and Schneider, D. (1988). Carrier-mediated uptake of pyrrolizidine alkaloids in larvae of the aposematic and alkaloid-exploiting moth Creatonotus. Naturwissenschaften 75 524-525. 

Synaptic serotonin (5-hydroxytryptamine) transporters are inhibited by amphetamines, the tropane alkaloids cocaine and ecgonine [194] and by the indole alkaloid ibogaine (12-methoxyibogamine) and its demethylation product ibogamine [191, 195]. Hyperforin is a major antidepressant constituent of St. John s Wort (Hypericum perforatum) and inhibits serotonin uptake by elevating cytosolic Na+ [196]. The additional... 

Mende, P. and Wink, M. 1987. Uptake of the quinolizidine alkaloid lupanine by protoplasts and isolated vacuoles of suspension-cultured Lupinus polyphyllus cells. Diffusion or carrier-mediated transport J. Plant Physiol. 129, 229-242... 

Wink, M. and Mende, P. 1987. Uptake of lupanine by alkaloid-storing epidermal cells of Lupinus polyphyllus. Planta Medica 53, 465-469... 

The non-specific tritiation of papaverine ha been described,13 as have methods for the detection of the alkaloid in body fluids.1415 The effects of papaverine on the biochemical fate of thymidine phosphate in the thymus,16 on cyclic AMP and the uptake of calcium in isolated pig auricle,17 on the monosynaptic reflex,18 on the L-DOPA-influenced secretion of GH and PRL,19 on cerebral blood flow,20 and on longitudinal smooth muscle21 have been studied, as have the /3-receptor-stimulant... 

A third strategy for coping with accumulated PAs is realized by larvae of Arctiidae moths. As in unadapted herbivores, PA A-oxides present in the larval diet are efficiently reduced in the gut. Due to their lipophilic properties, these alkaloids are easily resorbed into the hemolymph. To detoxify and to trap them in a non-toxic, hydrophilic form they are efficiently A-oxidized in the larval hemolymph and subsequently distributed to all tissues. Based on feeding experiments with senecionine [l80]A-oxide, an A-oxide-specific carrier for the direct uptake of plant derived A-oxides into the hemolymph was excluded.48 All labeled senecionine was recovered in the hemolymph as [16OJA-oxide. The same phenomenon was demonstrated for the grasshopper Zonocerus variegatus (Orthoptera).48... 

VON BORSTEL, K., HARTMANN, T., Selective uptake of pyrrolizidine V-oxides by cell suspension cultures from pyrrolizidine alkaloid producing plants. Plant Cell Rep., 1986,5,39-42. 

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