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Application of Pharmacological Approaches to Plant–Mammal Interactions

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Abstract

The dominant theory in the field of mammalian herbivore–plant interactions is that intake, and therefore tolerance, of plant secondary metabolites (PSMs) is regulated by mechanisms that reduce absorption and increase detoxification of PSMs. Methods designed by pharmacologists to measure detoxification enzyme activity, metabolite excretion, and most recently, drug absorption, have been successfully applied by ecologists to study PSM intake in a variety of mammalian study systems. Here, we describe several pharmacological and molecular techniques used to investigate the fate of drugs in human that have potential to further advance knowledge of mammalian herbivore–plant interactions.

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References

  • Ambudkar, S. V., Kimchi-Sarfaty, C., Sauna, Z. E., and Gottesman, M. M. 2003. P-glycoprotein: from genomics to mechanism. Oncogene 22:7468–7485.

    Article  PubMed  CAS  Google Scholar 

  • Appendino, G., Porta, C. D., Conseil, G., Sterner, O., Mercalli, E., Dumontet, C., and Di Peitro, A. 2003. A new P-glycoprotein inhibitor from the caper spurge (Euphorbia lathyris). J. Nat. Prod. 66:140–142.

    Article  PubMed  CAS  Google Scholar 

  • Ayrton, A. and Morgan, P. 2001. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 31:469–497.

    Article  PubMed  CAS  Google Scholar 

  • Barbehenn, R. 2001. Roles of peritrophic membranes in protecting herbivorous insects from ingested plant allelochemicals. Arch. Insect Biochem. Physiol. 47:86–99.

    Article  PubMed  CAS  Google Scholar 

  • Bard, S. M., Bello, S. M., Hahn, M. E., and Stegeman, J. J. 2002. Expression of P-glycoprotein in killifish (Fundulus heteroclitus) exposed to environmental xenobiotics. Aquat. Toxicol. 59:237–251.

    Article  PubMed  CAS  Google Scholar 

  • Barnes, D. M. 2001. Expression of P-glycoprotein in the chicken. Comp. Biochem. Physiol. A 130:301–310.

    Article  CAS  Google Scholar 

  • Belin, D. 1998. The use of RNA probes for the analysis of gene expression: Northern blot hybridization and ribonuclease protection assay, pp. 87–102, in R. Rapley and D. L. Manning (eds.). Methods in Molecular Biology; RNA Isolation and Characterization Protocols. Humana Press Inc., Totowa, NJ.

    Google Scholar 

  • Bellamy, W. T. 1996. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmacol. Toxicol. 36:161–183.

    Article  PubMed  CAS  Google Scholar 

  • Benet, L. and Cummins, C. 2001. The drug efflux-metabolism alliance: biochemical aspects. Adv. Drug Deliv. Rev. 50:S3–S11.

    Article  PubMed  CAS  Google Scholar 

  • Benet, L., Izumi, T., Zhang, Y., Silverman, J. A., and Wacher, V. 1999. Intestinal MDR transport proteins and P-450 enzymes as barriers to oral drug delivery. J. Control. Rel. 62:25–31.

    Article  PubMed  CAS  Google Scholar 

  • Berenbaum, M. R. 1999. Animal–plant warfare: molecular basis for cytochrome P450-mediated natural adaptation, pp. 553–571, in A. Puga and K. Wallace, (eds). Molecular Biology of the Toxic Response. Taylor and Francis, Philadelphia, PA.

    Google Scholar 

  • Bjornsson, T. D., Callaghan, J. T., Einolf, H. J., Fischer, V., Gan, L., Grimm, S., Kao, J., King, S. P., Miwa, G., Ni, L., Kumar, G., McLeod, J., Obach, R. S., Roberts, S., Roe, A., Shah, A., Snikeris, F., Sullivan, J. T., Tweedie, D., Vega, J. M., Walsh, J., and Wrighton, S. A. 2003. The conduct of in vitro and in vivo drug–drug interaction studies: a pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metab. Dispos. 31:815–832.

    Article  PubMed  CAS  Google Scholar 

  • Bock, K. W. and Köhle, C. 2004. Coordinate regulation of drug metabolism by xenobiotic nuclear receptors: UGTs acting together with CYPs and glucuronide transporters. Drug Metab. Rev. 36:595.

    Article  PubMed  CAS  Google Scholar 

  • Bolton, R. M. and Ahokas, J. T. 1997a. Mixed function oxidases in an Australian marsupial, the brushtail possum (Trichosurus vulpecula). Arch. Environ. Contam. Toxicol. 33:83–89.

    Article  PubMed  CAS  Google Scholar 

  • Bolton, R. M. and Ahokas, J. T. 1997b. Ontogenic Expression of Detoxication Enzymes in an Australian Marsupial, the Brushtail Possum (Trichosurus vulpecula). Comp. Biochem. Physiol. 18B:239.

    Google Scholar 

  • Boroujerdi, M. 2001. Pharmacokinetics—Principles and Applications. McGraw-Hill, New York.

    Google Scholar 

  • Boyle, R., McLean, S., Davies, N., Foley, W., and Moore, B. 1999a. Folivorous specialization: adaptations in the detoxification of the dietary terpene, p-cymene, in Australian marsupial folivores. Am. Zool. 39:120A.

    Google Scholar 

  • Boyle, R., McLean, S., Foley, W. J., and Davies, N. W. 1999b. Comparative metabolism of dietary terpene, p-cymene, in generalist and specialist folivorous marsupials. J. Chem. Ecol. 25:2109–2126.

    Article  CAS  Google Scholar 

  • Boyle, R. R. and McLean, S. 2004. Constraint of feeding by chronic ingestion of 1,8-cineole in the brushtail possum (Trichosurus vulpecula). J. Chem. Ecol. 30:757–775.

    Article  PubMed  CAS  Google Scholar 

  • Brayden, D. J. 1997. Human intestinal epithelial cell monolayers as prescreens for oral drug delivery. Pharm. News 4:11–15.

    CAS  Google Scholar 

  • Buss, D. S., McCaffery, A. R., and Callaghan, A. 2002. Evidence for p-glycoprotein modification of insecticide toxicity in mosquitoes of the Culex pipiens complex. Med. Vet. Entomol. 16:218–222.

    Article  PubMed  CAS  Google Scholar 

  • Chan, L. M. S., Lowes, S., and Hirst, B. H. 2004. The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur. J. Pharm. Sci. 21:25–51.

    Article  PubMed  CAS  Google Scholar 

  • Churchill, G. A. 2002. Fundamentals of experimental design for cDNA microarrays. Nat. Genet. 32(Suppl):490.

    Article  PubMed  CAS  Google Scholar 

  • Davies, B. and Morris, T. 1993. Physiological parameters in laboratory animals and humans. Pharm. Res. 10:1093–1095.

    Article  PubMed  CAS  Google Scholar 

  • Dearing, M. D., Foley, W. J., and McLean, S. 2005. The influence of plant secondary metabolites in the nutritional ecology of herbivorous terrestrial vertebrates. Ann. Rev. Ecolog. Evol. Syst. 36:169–189.

    Article  Google Scholar 

  • Dietrich, C. G., Geier, A., and Oude Elferink, R. P. J. 2003. ABC of oral bioavailability: transporters as gatekeepers in the gut. Gut 52:1788–1795.

    Article  PubMed  CAS  Google Scholar 

  • Doi, A. M., Holmes, E., and Kleinow, K. M. 2001. P-glycoprotein in the catfish intestine: inducibility by xenobiotics and functional properties. Aquat. Toxicol. 55:157–170.

    Article  PubMed  CAS  Google Scholar 

  • Dudler, R. and Hertig, C. 1992. Structure of an mdr-like gene from Arabidopsis thaliana. J. Biol. Chem. 267:5882–5888.

    PubMed  CAS  Google Scholar 

  • Enard, W., Khaitovich, P., Klose, J., Zöllner, S., Heissig, F., Giavalisco, P., Nieselt-Struwe, K., Muchmore, E., Varki, A., Ravid, R., Doxiadis, G. M., Bontrop, R. E., and Pääbo, S. 2002. Intra- and interspecific variation in primate gene expression patterns. Science 296:340.

    Article  PubMed  CAS  Google Scholar 

  • Freeland, W. J. and Janzen, D. H. 1974. Strategies in herbivory by mammals: the role of plant secondary compounds. Am. Nat. 108:269–289.

    Article  CAS  Google Scholar 

  • Fromm, M. 2004. Importance of P-glycoprotein at blood–tissue barriers. Trends Pharmacol. Sci. 25:423–429.

    Article  PubMed  CAS  Google Scholar 

  • Fromm, M. F. 2003. Importance of P-glycoprotein for drug disposition in humans. Eur. J. Clin. Investig. 33:6–9.

    Article  CAS  Google Scholar 

  • Fröhlich, M., Albermann, S., Sauer, A., Walter-Sack, I., Haefeli, W. E., and Weiss, J. 2004. In vitro and ex vivo evidence for modulation of P-glycoprotein activity by progestins. Biochem. Pharmacol. 68:2409–2416.

    Article  PubMed  CAS  Google Scholar 

  • Gardmo, C., Kotokorpi, P., Helander, H., and Mode, A. 2005. Transfection of adult primary rat hepatocytes in culture. Biochem. Pharmacol. 69:1805–1813.

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi, M. and Perrier, D. 1982. Pharmacokinetics. Marcel Dekker, New York.

    Google Scholar 

  • Gibson, G. 2002. Microarrays in ecology and evolution: A preview. Mol. Ecol. 11:17–24.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez, F. J. and Nebert, D. W. 1990. Evolution of the P450 gene superfamily: animal–plant ‘warfare’, molecular drive and human genetic differences in drug oxidation. Trends Genet. 6:182.

    Article  PubMed  CAS  Google Scholar 

  • Gracey, A. Y. and Cossins, A. R. 2003. Application of microarray technology in environmental and comparative physiology. Annu. Rev. Physiol. 65:231.

    Article  PubMed  CAS  Google Scholar 

  • Green, A. K., Haley, S., Dearing, M. D., Barnes, D. M., and Karasov, W. H. 2004. Intestinal capacity of P-glycoprotein is higher in the juniper specialist, Neotoma stephensi, than the sympatric generalist, Neotoma albigula. Comp. Biochem. Physiol. 139A:325–333.

    CAS  Google Scholar 

  • Green, A. K., Barnes, D. M., and Karasov, W. H. 2005. A new method to measure intestinal activity of P-glycoprotein in avian and mammalian species. J. Comp. Physiol. 175B:57–66.

    Google Scholar 

  • Grotenhermen, F. 2005. Cannabinoids. Curr. Drug Targets CNS Neurol. Disord. 4:507–530.

    Article  PubMed  CAS  Google Scholar 

  • Hayes, A. W. 2001. Principles and Methods of Toxicology. Taylor & Francis, Philadelphia.

    Google Scholar 

  • Hohmann, J., Molnar, J., Redei, D., Evanics, F., Forgo, P., Kalman, A., Argay, G., and Szabo, P. 2002. Discovery and biological evaluation of a new family of potent modulators of multidrug resistance: reversal of multidrug resistance of mouse lymphoma cells by new natural jatrophane diterpenoids isolated from Euphorbia species. J. Med. Chem. 45:2425–2431.

    Article  PubMed  CAS  Google Scholar 

  • Hollenberg, P. F. 2002. Characteristics and common properties of inhibitors, inducers, and activators of CYP enzymes. Drug Metab. Rev. 34:17.

    Article  PubMed  CAS  Google Scholar 

  • Hunter, J. and Hirst, B. 1997. Intestinal secretion of drugs. The role of P-glycoprotein and related drug efflux systems in limiting oral drug absorption. Adv. Drug Deliv. Rev. 25:129–157.

    Article  CAS  Google Scholar 

  • Jung'a, J. O., Mitema, E. S., and Gutzeit, H. O. 2005. Establishment and comparative analyses of different culture conditions of primary hepatocytes from Nile tilapia (Oreochromis niloticus) as a model to study stress induction in vitro. In Vitro Cell. Dev. Biol., Anim. 41:1–6.

    Google Scholar 

  • Karban, R. and Agrawal, A. A. 2002. Herbivore offense. Annu. Rev. Ecolog. Syst. 33:641–664.

    Article  Google Scholar 

  • Keppler, C. J. and Ringwood, A. H. 2001. Expression of P-glycoprotein in southeastern oysters, Crassostrea virginica. Mar. Environ. Res. 52:81–96.

    Article  PubMed  CAS  Google Scholar 

  • Khatri, P. and Drăghici, S. 2005. Ontological analysis of gene expression data: current tools, limitations, and open problems. Bioinformatics 21:3587.

    Article  PubMed  CAS  Google Scholar 

  • Kim, E. J. and Shin, W. H. 2005. General pharmacology of CKD-732, a new anticancer agent: effects on central nervous, cardiovascular, and respiratory system. Biol. Pharm. Bull. 28:217–223.

    Article  PubMed  CAS  Google Scholar 

  • Klaasen, C. D. and Watkins, J. B. 2003. Casarett & Doull's Essentials of Toxicology. McGraw-Hill, New York.

    Google Scholar 

  • Klaper, R. and Thomas, M. A. 2004. At the crossroads of genomics and ecology: the promise of a canary on a chip. Bioscience 54:403–412.

    Google Scholar 

  • Koizumi, T., Maeda, H., and Hioki, K. 2001. Sleep-time variation for ethanol and the hypnotic drugs tribomoethanol, urethane, pentobarbital, and propofol within outbred ICR mice. Exp. Anim. 51:119–124.

    Article  Google Scholar 

  • Konishi, H., Morita, K., Minouchi, T., and Yamaji, A. 2002. Moricizine, an antiarrhythmic agent, as a potent inhibitor of hepatic microsomal CYP1A. Pharmacology 66:190–198.

    Article  PubMed  CAS  Google Scholar 

  • Lamb, J. G., Sorensen, J. S., and Dearing, M. D. 2001. Comparison of detoxification enzyme mRNAs in woodrats (Neotoma lepida) and laboratory rats. J. Chem. Ecol. 27:845–857.

    Article  PubMed  CAS  Google Scholar 

  • Lamb, J. G., Marick, P., Sorensen, J., Haley, S., and Dearing, M. D. 2004. Liver biotransforming enzymes in woodrats Neotoma stephensi (Muridae). Comp. Biochem. Physiol. 138C:195–201.

    CAS  Google Scholar 

  • Lanning, C. L., Ayad, H. M., and Abou-Donia, M. B. 1996a. P-glycoprotein involvement in cuticular penetrations of [14C] theidicarb in resistant tobacco budworms. Toxicol. Lett. 85:127–133.

    Article  PubMed  CAS  Google Scholar 

  • Lanning, C. L., Fine, R. L., Corcoran, J. J., Ayad, H. M., Rose, R. L., and Abou-Donia, M. B. 1996b. Tobacco budworm P-glycoprotein: biochemical characterization and its involvement in pesticide resistance. Biochim. Biophys. Acta 1291:155–162.

    PubMed  Google Scholar 

  • Lawler, I. R., Foley, W. J., Pass, G. J., and Eschler, B. M. 1998. Administration of a 5HT3 receptor antagonist increases the intake of diets containing Eucalyptus secondary metabolites by marsupials. J. Comp. Physiol. 168B:611.

    Google Scholar 

  • LeCluyse, E. L. 2001. Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur. J. Pharm. Sci. 13:343–368.

    Article  PubMed  CAS  Google Scholar 

  • Lee, G., Schlichter, L., Bendayan, M., and Bendayan, R. 2001. Functional expression of P-glycoprotein in rat brain microglia. Pharmacol. Exp. Ther. 299:204–212.

    CAS  Google Scholar 

  • Lehane, M. 1997. Peritrophic matrix structure and function. Annu. Rev. Entomol. 42:525–550.

    Article  PubMed  CAS  Google Scholar 

  • Li, X., Baudry, J., Berenbaum, M. R., and Schuler, M. A. 2004. Structural and functional divergence of insect CYP6B proteins: From specialist to generalist cytochrome P450. Proc. Nat. Acad. Sci. U. S. A. 101:2939.

    Article  CAS  Google Scholar 

  • Liapis, P., Pass, G. J., McKinnon, R. A., and Stupans, I. 2000. Characterisation of tolbutamide hydroxylase activity in the common brushtail possum, (Trichosurus vulpecula) and koala (Phascolarctos cinereus): inhibition by the eucalyptus terpene 1,8-cineole. Comp. Biochem. Physiol. 127:351.

    CAS  Google Scholar 

  • Liminga, G., Nygren, P., and Larsson, R. 1994. Microfluorometric evaluation of calcein acetoxymethyl ester as a probe for P-glycoprotein-mediated resistance: effects of cyclosporin A and its nonimmunosuppressive analogue SDZ PSC 833. Exp. Cell. Res. 212:291–296.

    Article  PubMed  CAS  Google Scholar 

  • Lin, J. H. and Yamazaki, M. 2003a. Clinical relevance of P-glycoprotein in drug therapy. Drug Metab. Rev. 35:417–454.

    Article  PubMed  CAS  Google Scholar 

  • Lin, J. H. and Yamazaki, M. 2003b. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet. 43:59–98.

    Article  Google Scholar 

  • Litman, T., Zeuthen, T., Skovsgaard, T., and Stein, W. D. 1997. Structure–activity relationships of P-glycoprotein interacting drugs: kinetic characterization of their effects on ATPase activity. Biochem. Biophys. Acta 1361:159–168.

    PubMed  CAS  Google Scholar 

  • Mangione, A. M., Dearing, D., and Karasov, W. 2001. Detoxification in relation to toxin tolerance in desert woodrats eating creosote bush. J. Chem. Ecol. 27:2559.

    Article  PubMed  CAS  Google Scholar 

  • Mankowski, D. C., Laddison, K. J., Christopherson, P. A., S. E., Tweedie, D. J., and Lawton, M. P. 1999. Molecular cloning, expression, and characterization of CYP2D17 from cynomolgus monkey liver. Arch. Biochem. Biophys. 372:189–196.

    Article  PubMed  CAS  Google Scholar 

  • McArthur, C., Sanson, G. D., and Beal, A. M. 1995. Salivary proline-rich proteins in mammals: roles in oral homeostasis and counteracting dietary tannin. J. Chem. Ecol. 21:663–691.

    Article  CAS  Google Scholar 

  • McLean, S., Pass, G. J., Foley, W. J., Brandon, S., and Davies, N. W. 2001. Does excretion of secondary metabolites always involve a measurable metabolic cost? Fate of plant antifeedant salicin in common brushtail possum, Trichosurus vulpecula. J. Chem. Ecol. 27:1077.

    Article  PubMed  CAS  Google Scholar 

  • McManus, M. E. and Ilett, K. F. 1977. Microsomal xenobiotic metabolism in marsupials. Drug Metab. Dispos. 5:503–510.

    PubMed  CAS  Google Scholar 

  • Melaine, N., Lienard, M., Dorval, I., Le Goascogne, C., Lejeune, H., and Jegou, B. 2002. Multidrug Resistance Genes and P-Glycoprotein in the Testis of the Rat, Mouse, Guinea Pig, and Human. Biol. Reprod. 67:1699–1707.

    Article  PubMed  CAS  Google Scholar 

  • Meyer, U. A. 2004. Pharmacogenetics—five decades of therapeutic lessons from genetic diversity. Nat. Rev. 5:669.

    CAS  Google Scholar 

  • Meyer, U. A. and Gut, J. 2002. Genomics and the prediction of xenobiotic toxicity. Toxicology 181–182:463.

    Article  PubMed  Google Scholar 

  • Moody, D. E., Zou, Z., and McIntyre, L. 2002. Cross-species hybridisation of pig RNA to human nylon microarrays. BMC Genomics 3:27.

    Article  PubMed  CAS  Google Scholar 

  • Murray, C. L., Quaglia, M., Arnason, J. T., and Morris, C. E. 1994. A putative nicotine pump at the metabolic blood–brain-barrier of the tobacco hornworm. J. Neurobiol. 25:23–34.

    Article  PubMed  CAS  Google Scholar 

  • Nebert, D. W. and Dieter, M. Z. 2000. The evolution of drug metabolism. Pharmacology 61:124–135.

    Article  PubMed  CAS  Google Scholar 

  • Nebert, D. W. and Roe, A. L. 2001. Ethnic and genetic differences in metabolism genes and risk of toxicity and cancer. Sci. Total Environ. 274:93–102.

    Article  PubMed  CAS  Google Scholar 

  • Neubig, R. R. 1990. The time course of drug action, pp. 297–364, in W. B. Pratt and P. T. Taylor, (eds). Principles of Drug Action: The Basis of Pharmacology. Churchill Livingston, Philadelphia.

    Google Scholar 

  • Newton, D. J., Wang, R. W., and Lu, A. Y. 1995. Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab. Dispos. 23:154–158.

    PubMed  CAS  Google Scholar 

  • Ngo, S., Kong, S., Kirlich, A., McKinnon, R. A., and Stupans, I. 2000. Cytochrome P450 4A, peroxisomal enzymes and nicotinamide cofactors in koala liver. Comp. Biochem. Physiol. 127:327.

    CAS  Google Scholar 

  • Ngo, S. N. T., McKinnon, R. A., and Stupans, I. 2003. The effects of Eucalyptus terpenes on hepatic cytochrome P450 CYP4A, peroxisomal Acyl CoA oxidase (AOX) and peroxisome proliferator activated receptor alpha (PPARalpha) in the common brush tail possum (Trichosurus vulpecula). Comp. Biochem. Physiol. 136:165.

    Google Scholar 

  • Oliveira, F. A., Costa, C. L., Chaves, M. H., Almeida, F. R., Cavalcante, I. J., Lima, A. F., Lima, R. C., Jr., Silva, R. M., Campos, A. R., Santos, F. A., and Rao, V. S. 2005. Attenuation of capsaicin-induced acute and visceral nociceptive pain by alpha- and beta-amyrin, a triterpene mixture isolated from Protium heptaphyllum resin in mice. Life Sci. 77:2942–2952.

    Article  PubMed  CAS  Google Scholar 

  • Pass, G. J. and McLean, S. 2002. Inhibition of the microsomal metabolism of 1,8-cineole in the common brushtail possum (Trichosurus vulpecula) by terpenes and other chemicals. Xenobiotica 32:1109–1126.

    Article  PubMed  CAS  Google Scholar 

  • Pass, G. J., McLean, S., and Stupans, I. 1999. Induction of xenobiotic metabolising enzymes in the common brushtail possum, Trichosurus vulpecula, by Eucalyptus terpenes. Comp. Biochem. Physiol. 124:239.

    PubMed  CAS  Google Scholar 

  • Pass, G. J., McLean, S., Stupans, I., and Davies, N. 2001. Microsomal metabolism of the terpene 1,8-cineole in the common brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus), rat and human. Xenobiotica 31:205.

    Article  PubMed  CAS  Google Scholar 

  • Pass, G. J., McLean, S., Stupans, I., and Davies, N. W. 2002. Microsomal metabolism and enzyme kinetics of the terpene p-cymene in the common brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus) and rat. Xenobiotica 32:383–397.

    Article  PubMed  CAS  Google Scholar 

  • Polli, J. W., Wring, S. A., Humphreys, J. E., Huang, L., Morgan, J. B., Webster, L. O., and Serabjit-Singh, C. S. 2001. Rational use of in vitro P-glycoprotein assays in drug discovery. J. Pharmacol. Exp. Ther. 299:620–628.

    PubMed  CAS  Google Scholar 

  • Puga, A., Nebert, D. W., McKinnon, R. A., and Menon, A. G. 1997. Genetic polymorphisms in human drug-metabolizing enzymes: Potential uses of reverse genetics to identify genes of toxicological relevance. Crit. Rev. Toxicol. 27:199–222.

    PubMed  CAS  Google Scholar 

  • Reiner, A., Yekutieli, D., and Benjamini, Y. 2003. Identifying differentially expressed genes using false discovery rate controlling procedures. Bioinformatics 19:368.

    Article  PubMed  CAS  Google Scholar 

  • Rosenthal, G. A. and Berenbaum, M. R. 1992. Herbivores: Their Interaction with Secondary Plant Metabolites. Academic Press, New York.

    Google Scholar 

  • Sabelli, P. A. 1998. Northern blot analysis, pp. 89–93 in R. Rapley and J. M. Walker (eds.). Molecular Biomethods Handbook. Humana Press Inc., Totowa, NJ.

    Google Scholar 

  • Saier, M. H. J. and Paulsen, I. T. 2001. Phylogeny of multidrug transporters. Cell Dev. Biol. 12:205–213.

    Article  CAS  Google Scholar 

  • Samara, E., Bialer, M., and Mechoulam, R. 1988. Pharmacokinetics of cannabidiol in dogs. Drug Metab. Dispos. 16:469–472.

    PubMed  CAS  Google Scholar 

  • Sangster, N. C. 1994. P-glycoproteins in nematodes. Parasitol. Today 10:319–322.

    Article  PubMed  CAS  Google Scholar 

  • Sasaki, N. 1994. Effects of furazolidone on duration of righting reflex loss induced with hexobarbital and zoxazolamine in the rat. J. Vet. Med. Sci. 56:667–670.

    PubMed  CAS  Google Scholar 

  • Sasaki, T., Ezaki, B., and Matsumoto, H. 2002. A gene encoding multidrug resistance (MDR)-like protein is induced by aluminum and inhibitors of calcium flux in wheat. Plant Cell Physiol. 43:177–185.

    Article  PubMed  CAS  Google Scholar 

  • Scarborough, G. A. 1995. Drug-stimulated ATPase activity of the human P-glycoprotein. J. Bioenerg. Biomembranes 27:37–41.

    Article  CAS  Google Scholar 

  • Scheffer, G. L., Kool, M., Heijn, M., De Haas, M., Pijnenborg, A. C. L. M., Wijnholds, J., Van Helvoort, A., De Jong, M. C., Hooijberg, J. H., Mol, C. A. A. M., Van Der Linden, M., De Vree, J. M. L., Van der Valk, P., Elferink, R. P. J. O., Borst, P., and Scheper, R. J. 2000. Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 p-glycoprotein with a panel of monoclonal antibodies. Cancer Res. 60:5269–5277.

    PubMed  CAS  Google Scholar 

  • Schinkel, A. H. 1999. P-glycoprotein, a gatekeeper in the blood–brain barrier. Adv. Drug Deliv. Rev. 36:179–194.

    Article  PubMed  CAS  Google Scholar 

  • Schinkel, A. H. and Jonker, J. W. 2003. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv. Drug Deliv. Rev. 55:3–29.

    Article  PubMed  CAS  Google Scholar 

  • Schmid, D., Ecker, G., Kopp, S., Hitzler, M., and Chiba, P. 1999. Structure–activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements. Biochem. Pharmacol. 58:1447–1456.

    Article  PubMed  CAS  Google Scholar 

  • Seelig, A. 1998. A general pattern for substrate recognition by P-glycoprotein. Eur. J. Biochem. 251:252–261.

    Article  PubMed  CAS  Google Scholar 

  • Seelig, A. and Landwojtowicz, E. 2000. Structure–activity relationship of P-glycoprotein substrates and modifiers. Eur. J. Pharm. Sci. 12:31–40.

    Article  PubMed  CAS  Google Scholar 

  • Sharom, F. 1997. The P-glycoprotein efflux pump: how does it transport drugs? J. Membr. Biol. 160:161–175.

    Article  PubMed  CAS  Google Scholar 

  • Silverman, J. A. 1999. Multidrug-resistance transporters. Pharm. Biotechnol. 12:353–386.

    Article  PubMed  CAS  Google Scholar 

  • Skopec, M. M., Hagerman, A. E., and Karasov, W. H. 2004. Do salivary proline-rich proteins counteract dietary hydrolyzable tannin in laboratory rats? J. Chem. Ecol. 30:1679–1692.

    Article  PubMed  CAS  Google Scholar 

  • Smith, J. M. and Prichard, R. K. 2002. Localization of p-glycoprotein mRNA in the tissues of Haemonchus contortus adult worms and its relative abundance in drug-selected and susceptible strains. J. Parasitol. 88:612–620.

    Article  PubMed  CAS  Google Scholar 

  • Sorensen, J. S. and Dearing, M. D. 2003. Elimination of plant toxins by herbivorous woodrats: revisiting an explanation for dietary specialization in mammalian herbivores. Oecologia 134:88–94.

    Article  PubMed  CAS  Google Scholar 

  • Sorensen, J. S. and Dearing, M. D. 2006. JCE, this issue. Efflux transporters as a novel herbivore defense to plant chemical defenses. J. Chem. Ecol. (in press).

  • Sorensen, J. S., Turnbull, C. A., and Dearing, M. D. 2004. A specialist herbivore (Neotoma stephensi) absorbs fewer plant toxins than does a generalist (Neotoma albigula). Physiol. Biochem. Zool. 77:139–148.

    Article  PubMed  CAS  Google Scholar 

  • Sparreboom, A., Danesi, R., Ando, Y., Chan, J., and Figg, W. D. 2003. Pharmacogenomics of ABC transporters and its role in cancer chemotherapy. Drug Resist. Updat. 2:71–84.

    Article  CAS  Google Scholar 

  • Stein, W. D. 1997. Kinetics of the multidrug transporter (P-glycoprotein) and its reversal. Pharmacol. Rev. 77:575–590.

    Google Scholar 

  • Stupans, I., Kong, S., Kirlich, A., Murray, M., Bailey, E. L., Jones, B. R., and McKinnon, R. A. 1999. Hepatic microsomal enzyme activity in the koala and tammar wallaby: high 17beta-hydroxysteroid oxidoreductase activity in koala liver microsomes. Comp. Biochem. Physiol. 123:67.

    Article  CAS  Google Scholar 

  • Stupans, I., Jones, B., and McKinnon, R. A. 2001. Xenobiotic metabolism in Australian marsupials. Comp. Biochem. Physiol. 128:367.

    CAS  Google Scholar 

  • Thomas, M. A. and Klaper, R. 2004. Genomics for the ecological toolbox. Trends Ecol. Evol. 19:439–445.

    Article  PubMed  Google Scholar 

  • Tiberghien, F. and Loor, F. 1996. Ranking of P-glycoprotein substrates and inhibitors by calcein-AM fluorometry screening assay. Anticancer Drugs 7:568–578.

    PubMed  CAS  Google Scholar 

  • Tittiger, C. 2004. Functional genomics and insect chemical ecology. J. Chem. Ecol. 30:2335–2358.

    Article  PubMed  CAS  Google Scholar 

  • Tucker, G. T., Houston, J. B., and Huang, S. M. 2001. Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential-toward a consensus. Clin. Pharmacol. Ther. 70:103–114.

    Article  PubMed  CAS  Google Scholar 

  • von Richter, O., Burk, O., Fromm, M., Thon, K., Eichelbaum, M., and Kivisto, K. 2004. Cytochrome P450 3A4 and P-glycoprotein expression in human small intestinal enterocytes and hepatocytes: a comparative analysis in paired tissue specimens. Clin. Pharmacol. Ther. 75:172–183.

    Article  PubMed  CAS  Google Scholar 

  • Wada, K., Sasaki, K., Miura, K. I., Yagi, M., Kubota, Y., Matsumoto, T., and Haga, M. 1993. Isolation of bilobalide and ginkgolide A from Ginkgo biloba L shorten the sleeping time induced in mice by anesthetics. Biol. Pharm. Bull. 16:210–212.

    PubMed  CAS  Google Scholar 

  • Washington, N., Washington, C., and Wilson, C. G. 2001. Physiological Pharmaceutics: Barriers to Drug Absorption. Taylor and Francis Inc., New York.

    Google Scholar 

  • Watkins, P. B. 1997. The barrier function of CYP3A4 nd P-glycoprotein in the small bowel. Adv. Drug Deliv. Rev. 27:161–170.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, J., Dormann, S. M. G., Martin-Facklam, M., Kerpen, C. J., Ketabi-Kiyanvash, N., and Haefeli, W. E. 2003. Inhibition of P-glycoprotein by newer antidepressants. J. Pharmacol. Exp. Ther. 305:197–204.

    Article  PubMed  CAS  Google Scholar 

  • Wong, M. L. and Medrano, J. F. 2005. Real-time PCR for mRNA quantitation. BioTechniques 39:75.

    Article  PubMed  CAS  Google Scholar 

  • Woo, Y., Affourtit, J., Daigle, S., Viale, A., Johnson, K., Naggert, J., and Churchill, G. 2004. A comparison of cDNA, oligonucleotide, and Affymetrix GeneChip gene expression microarray platforms. J. Biomol. Tech. 15:276.

    PubMed  Google Scholar 

  • Yang, M. C. K., Yang, J. J., McIndoe, R. A., and She, J. X. 2003. Microarray experimental design: power and sample size considerations. Physiol. Genomics 16:24.

    Article  PubMed  CAS  Google Scholar 

  • Yazaki, K., Shitan, N., Takamatsu, H., Ueda, K., and Sato, F. 2001. A novel Coptis japonica multidrug-resistant protein preferentially expressed in the alkaloid-accumulating rhizome. J. Exp. Bot. 52:877–879.

    PubMed  CAS  Google Scholar 

  • Zhang, Y. and Benet, L. Z. 2001. The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein. Clin. Pharmacokinet. 40:159–168.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, S., Lim, L., and Chowbay, B. 2004. Herbal modulation of P-glycoprotein. Drug Metab. Rev. 36:57–104.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Funding was provided by NSF International Research Fellowship INT-0301898 to J. S. Sorensen and NSF IBN0236402 to M. D. Dearing. We thank K. Smith for assistance with manuscript preparation. Two anonymous reviewers provided insightful comments. Finally, we thank R. Osawa, W. J. Foley, and T. Shimada for organizing a productive symposium at the IX International Mammalogical Congress in Sapporo, Japan, where these ideas were discussed.

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  1. Department of Biology, University of Utah, Salt Lake City, UT, 84112, USA

    Jennifer S. Sorensen, Michele M. Skopec & M. Denise Dearing

  2. NPS Pharmaceuticals, Salt Lake City, UT, 84108, USA

    Jennifer S. Sorensen

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  1. Jennifer S. Sorensen
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  2. Michele M. Skopec
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  3. M. Denise Dearing
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Correspondence to Jennifer S. Sorensen.

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Sorensen, J.S., Skopec, M.M. & Dearing, M.D. Application of Pharmacological Approaches to Plant–Mammal Interactions. J Chem Ecol 32, 1229–1246 (2006). https://doi.org/10.1007/s10886-006-9086-z

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  • DOI: https://doi.org/10.1007/s10886-006-9086-z

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