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Molecular Clocks in Pharmacology

Chapter
First Online:
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 217)

Abstract

Circadian rhythms regulate a vast array of biological processes and play a fundamental role in mammalian physiology. As a result, considerable diurnal variation in the pharmacokinetics, efficacy, and side effect profiles of many therapeutics has been described. This variation has subsequently been tied to diurnal rhythms in absorption, distribution, metabolism, and excretion, as well as in pharmacodynamic variables, such as target expression. More recently, the molecular basis of circadian rhythmicity has been elucidated with the identification of clock genes, which oscillate in a circadian manner in most cells and tissues and regulate transcription of large sets of genes. Ongoing research efforts are beginning to reveal the critical role of circadian clock genes in the regulation of pharmacologic parameters, as well as the reciprocal impact of drugs on circadian clock function. This chapter will review the role of circadian clocks in the pharmacokinetics and pharmacodynamics of drug response and provide several examples of the complex regulation of pharmacologic systems by components of the molecular circadian clock.

Keywords

Circadian clock Pharmacology Pharmacokinetics Pharmacodynamics CLOCK Bmal1 
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References

  1. Akashi M, Takumi T (2005) The orphan nuclear receptor ROR alpha regulates circadian transcription of the mammalian core-clock Bmal1. Nat Struct Mol Biol 12:441–448PubMedCrossRefGoogle Scholar
  2. Akashi M, Tsuchiya Y, Yoshino T, Nishida E (2002) Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKI epsilon) and CKIdelta in cultured cells. Mol Cell Biol 22:1693–1703PubMedCrossRefGoogle Scholar
  3. Ando H, Yanagihara H, Sugimoto K, Hayashi Y, Tsuruoka S, Takamura T, Kaneko S, Fujimura A (2005) Daily rhythms of P-glycoprotein expression in mice. Chronobiol Int 22:655–665PubMedCrossRefGoogle Scholar
  4. Angeli A, Frajria R, De Paoli R, Fonzo D, Ceresa F (1978) Diurnal variation of prednisolone binding to serum corticosteroid-binding globulin in man. Clin Pharmacol Ther 23:47–53PubMedGoogle Scholar
  5. Antoch MP, Gorbacheva VY, Vykhovanets O, Toshkov IA, Kondratov RV, Kondratova AA, Lee C, Nikitin AY (2008) Disruption of the circadian clock due to the Clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle 7:1197–1204PubMedCrossRefGoogle Scholar
  6. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, Schibler U (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134:317–328PubMedCrossRefGoogle Scholar
  7. Asher G, Reinke H, Altmeyer M, Gutierrez-Arcelus M, Hottiger MO, Schibler U (2010) Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell 142:943–953PubMedCrossRefGoogle Scholar
  8. Baggs JE, Price TS, DiTacchio L, Panda S, Fitzgerald GA, Hogenesch JB (2009) Network features of the mammalian circadian clock. PLoS Biol 7:e52PubMedCrossRefGoogle Scholar
  9. Bass J, Takahashi JS (2010) Circadian integration of metabolism and energetics. Science 330: 1349–1354PubMedCrossRefGoogle Scholar
  10. Belanger PM, Lalande M, Labrecque G, Dore FM (1985) Diurnal variations in the transferases and hydrolases involved in glucuronide and sulfate conjugation of rat liver. Drug Metab Dispos 13:386–389PubMedGoogle Scholar
  11. Belden WJ, Dunlap JC (2008) SIRT1 is a circadian deacetylase for core clock components. Cell 134:212–214PubMedCrossRefGoogle Scholar
  12. Bernard M, Klein DC, Zatz M (1997) Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in culture. Proc Natl Acad Sci USA 94:304–309PubMedCrossRefGoogle Scholar
  13. Bron R, Furness JB (2009) Rhythm of digestion: keeping time in the gastrointestinal tract. Clin Exp Pharmacol Physiol 36:1041–1048PubMedCrossRefGoogle Scholar
  14. Buhr ED, Takahashi JS (2013) Molecular components of the mammalian circadian clock. In: Kramer A, Merrow M (eds) Circadian clocks, vol 127, Handbook of experimental pharmacology. Springer, HeidelbergGoogle Scholar
  15. Cai Y, Ding H, Li N, Chai Y, Zhang Y, Chan P (2010) Oscillation development for neurotransmitter-related genes in the mouse striatum. Neuroreport 21:79–83PubMedCrossRefGoogle Scholar
  16. Canaple L, Rambaud J, Dkhissi-Benyahya O, Rayet B, Tan NS, Michalik L, Delaunay F, Wahli W, Laudet V (2006) Reciprocal regulation of brain and muscle Arnt-like protein 1 and peroxisome proliferator-activated receptor alpha defines a novel positive feedback loop in the rodent liver circadian clock. Mol Endocrinol 20:1715–1727PubMedCrossRefGoogle Scholar
  17. Cao QR, Kim TW, Choi JS, Lee BJ (2005) Circadian variations in the pharmacokinetics, tissue distribution and urinary excretion of nifedipine after a single oral administration to rats. Biopharm Drug Dispos 26:427–437PubMedCrossRefGoogle Scholar
  18. Cardone L, Hirayama J, Giordano F, Tamaru T, Palvimo JJ, Sassone-Corsi P (2005) Circadian clock control by SUMOylation of BMAL1. Science 309:1390–1394PubMedCrossRefGoogle Scholar
  19. Cermakian N, Lamont EW, Boudreau P, Boivin DB (2011) Circadian clock gene expression in brain regions of Alzheimer’s disease patients and control subjects. J Biol Rhythms 26:160–170PubMedCrossRefGoogle Scholar
  20. Charmandari E, Chrousos GP, Lambrou GI, Pavlaki A, Koide H, Ng SS, Kino T (2011) Peripheral CLOCK regulates target-tissue glucocorticoid receptor transcriptional activity in a circadian fashion in man. PLoS One 6:e25612PubMedCrossRefGoogle Scholar
  21. Cho H, Zhao X, Hatori M, Yu RT, Barish GD, Lam MT, Chong LW, DiTacchio L, Atkins AR, Glass CK, Liddle C, Auwerx J, Downes M, Panda S, Evans RM (2012) Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 485:123–127PubMedCrossRefGoogle Scholar
  22. Curtis AM, Seo SB, Westgate EJ, Rudic RD, Smyth EM, Chakravarti D, FitzGerald GA, McNamara P (2004) Histone acetyltransferase-dependent chromatin remodeling and the vascular clock. J Biol Chem 279:7091–7097PubMedCrossRefGoogle Scholar
  23. Davies MH, Bozigian HP, Merrick BA, Birt DF, Schnell RC (1983) Circadian variations in glutathione-S-transferase and glutathione peroxidase activities in the mouse. Toxicol Lett 19: 23–27PubMedCrossRefGoogle Scholar
  24. Deguchi T (1975) Ontogenesis of a biological clock for serotonin:acetyl coenzyme A N-acetyltransferase in pineal gland of rat. Proc Natl Acad Sci USA 72:2814–2818PubMedCrossRefGoogle Scholar
  25. Desai VG, Moland CL, Branham WS, Delongchamp RR, Fang H, Duffy PH, Peterson CA, Beggs ML, Fuscoe JC (2004) Changes in expression level of genes as a function of time of day in the liver of rats. Mutat Res 549:115–129PubMedCrossRefGoogle Scholar
  26. Dixit BN, Buckley JP (1967) Circadian changes in brain 5-hydroxytryptamine and plasma corticosterone in the rat. Life Sci 6:755–758PubMedCrossRefGoogle Scholar
  27. Doi M, Hirayama J, Sassone-Corsi P (2006) Circadian regulator CLOCK is a histone acetyltransferase. Cell 125:497–508PubMedCrossRefGoogle Scholar
  28. Dudley TE, DiNardo LA, Glass JD (1998) Endogenous regulation of serotonin release in the hamster suprachiasmatic nucleus. J Neurosci 18:5045–5052PubMedGoogle Scholar
  29. Edgar DM, Reid MS, Dement WC (1997) Serotonergic afferents mediate activity-dependent entrainment of the mouse circadian clock. Am J Physiol 273:R265–R269PubMedGoogle Scholar
  30. Eleftheriadis E, Kotzampassi K, Vafiadis M, Paramythiotis D (1998) 24-hr measurement of gastric mucosal perfusion in conscious humans. Hepatogastroenterology 45:2453–2457PubMedGoogle Scholar
  31. Etchegaray JP, Lee C, Wade PA, Reppert SM (2003) Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature 421:177–182PubMedCrossRefGoogle Scholar
  32. Gachon F, Olela FF, Schaad O, Descombes P, Schibler U (2006) The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab 4:25–36PubMedCrossRefGoogle Scholar
  33. Gallego M, Virshup DM (2007) Post-translational modifications regulate the ticking of the circadian clock. Nat Rev Mol Cell Biol 8:139–148PubMedCrossRefGoogle Scholar
  34. Glass JD, Grossman GH, Farnbauch L, DiNardo L (2003) Midbrain raphe modulation of nonphotic circadian clock resetting and 5-HT release in the mammalian suprachiasmatic nucleus. J Neurosci 23:7451–7460PubMedGoogle Scholar
  35. Golder SA, Macy MW (2011) Diurnal and seasonal mood vary with work, sleep, and day length across diverse cultures. Science 333:1878–1881PubMedCrossRefGoogle Scholar
  36. Goo RH, Moore JG, Greenberg E, Alazraki NP (1987) Circadian variation in gastric emptying of meals in humans. Gastroenterology 93:515–518PubMedGoogle Scholar
  37. Gumz ML, Stow LR, Lynch IJ, Greenlee MM, Rudin A, Cain BD, Weaver DR, Wingo CS (2009) The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice. J Clin Invest 119:2423–2434PubMedCrossRefGoogle Scholar
  38. Hampp G, Ripperger JA, Houben T, Schmutz I, Blex C, Perreau-Lenz S, Brunk I, Spanagel R, Ahnert-Hilger G, Meijer JH, Albrecht U (2008) Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr Biol 18:678–683PubMedCrossRefGoogle Scholar
  39. Harper DG, Volicer L, Stopa EG, McKee AC, Nitta M, Satlin A (2005) Disturbance of endogenous circadian rhythm in aging and Alzheimer disease. Am J Geriatr Psychiatry 13:359–368PubMedGoogle Scholar
  40. Hecquet B, Meynadier J, Bonneterre J, Adenis L, Demaille A (1985) Time dependency in plasmatic protein binding of cisplatin. Cancer Treat Rep 69:79–83PubMedGoogle Scholar
  41. Hirao J, Arakawa S, Watanabe K, Ito K, Furukawa T (2006) Effects of restricted feeding on daily fluctuations of hepatic functions including p450 monooxygenase activities in rats. J Biol Chem 281:3165–3171PubMedCrossRefGoogle Scholar
  42. Hirota T, Lewis WG, Liu AC, Lee JW, Schultz PG, Kay SA (2008) A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3beta. Proc Natl Acad Sci USA 105:20746–20751PubMedCrossRefGoogle Scholar
  43. Hirota T, Lee JW, Lewis WG, Zhang EE, Breton G, Liu X, Garcia M, Peters EC, Etchegaray JP, Traver D, Schultz PG, Kay SA (2010) High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKI alpha as a clock regulatory kinase. PLoS Biol 8:e1000559PubMedCrossRefGoogle Scholar
  44. Hirota T, Lee JW, St John PC, Sawa M, Iwaisako K, Noguchi T, Pongsawakul PY, Sonntag T, Welsh DK, Brenner DA, Doyle FJ 3rd, Schultz PG, Kay SA (2012) Identification of small molecule activators of cryptochrome. Science 337:1094–1097PubMedCrossRefGoogle Scholar
  45. Hoogerwerf WA (2006) Biologic clocks and the gut. Curr Gastroenterol Rep 8:353–359PubMedCrossRefGoogle Scholar
  46. Horikawa K, Yokota S, Fuji K, Akiyama M, Moriya T, Okamura H, Shibata S (2000) Nonphotic entrainment by 5-HT1A/7 receptor agonists accompanied by reduced Per1 and Per2 mRNA levels in the suprachiasmatic nuclei. J Neurosci 20:5867–5873PubMedGoogle Scholar
  47. Inoue N, Imai K, Aimoto T (1999) Circadian variation of hepatic glutathione S-transferase activities in the mouse. Xenobiotica 29:43–51PubMedCrossRefGoogle Scholar
  48. Inoue I, Shinoda Y, Ikeda M, Hayashi K, Kanazawa K, Nomura M, Matsunaga T, Xu H, Kawai S, Awata T, Komoda T, Katayama S (2005) CLOCK/BMAL1 is involved in lipid metabolism via transactivation of the peroxisome proliferator-activated receptor (PPAR) response element. J Atheroscler Thromb 12:169–174PubMedCrossRefGoogle Scholar
  49. Jaeschke H, Wendel A (1985) Diurnal fluctuation and pharmacological alteration of mouse organ glutathione content. Biochem Pharmacol 34:1029–1033PubMedCrossRefGoogle Scholar
  50. Kalsbeek A, Fliers E (2013) Daily regulation of hormone profiles. In: Kramer A, Merrow M (eds) Circadian clocks, vol 127, Handbook of experimental pharmacology. Springer, HeidelbergGoogle Scholar
  51. Kamali F, Fry JR, Bell GD (1987) Temporal variations in paracetamol absorption and metabolism in man. Xenobiotica 17:635–641PubMedCrossRefGoogle Scholar
  52. Kang HS, Angers M, Beak JY, Wu X, Gimble JM, Wada T, Xie W, Collins JB, Grissom SF, Jetten AM (2007) Gene expression profiling reveals a regulatory role for ROR alpha and ROR gamma in phase I and phase II metabolism. Physiol Genomics 31:281–294PubMedCrossRefGoogle Scholar
  53. Kino T, Chrousos GP (2011a) Acetylation-mediated epigenetic regulation of glucocorticoid receptor activity: circadian rhythm-associated alterations of glucocorticoid actions in target tissues. Mol Cell Endocrinol 336:23–30PubMedCrossRefGoogle Scholar
  54. Kino T, Chrousos GP (2011b) Circadian CLOCK-mediated regulation of target-tissue sensitivity to glucocorticoids: implications for cardiometabolic diseases. Endocr Dev 20:116–126PubMedGoogle Scholar
  55. Koh K, Evans JM, Hendricks JC, Sehgal A (2006) A Drosophila model for age-associated changes in sleep:wake cycles. Proc Natl Acad Sci USA 103:13843–13847PubMedCrossRefGoogle Scholar
  56. Kolker DE, Vitaterna MH, Fruechte EM, Takahashi JS, Turek FW (2004) Effects of age on circadian rhythms are similar in wild-type and heterozygous Clock mutant mice. Neurobiol Aging 25:517–523PubMedCrossRefGoogle Scholar
  57. Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP (2006) Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev 20:1868–1873PubMedCrossRefGoogle Scholar
  58. Konturek PC, Brzozowski T, Konturek SJ (2011) Gut clock: implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol 62:139–150PubMedGoogle Scholar
  59. Krajnak K, Rosewell KL, Duncan MJ, Wise PM (2003) Aging, estradiol and time of day differentially affect serotonin transporter binding in the central nervous system of female rats. Brain Res 990:87–94PubMedCrossRefGoogle Scholar
  60. Kumar D, Wingate D, Ruckebusch Y (1986) Circadian variation in the propagation velocity of the migrating motor complex. Gastroenterology 91:926–930PubMedGoogle Scholar
  61. Kume K, Zylka MJ, Sriram S, Shearman LP, Weaver DR, Jin X, Maywood ES, Hastings MH, Reppert SM (1999) mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98:193–205PubMedCrossRefGoogle Scholar
  62. Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326:437–440PubMedCrossRefGoogle Scholar
  63. Lamia KA, Papp SJ, Yu RT, Barish GD, Uhlenhaut NH, Jonker JW, Downes M, Evans RM (2011) Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature 480: 552–556PubMedGoogle Scholar
  64. Lavery DJ, Lopez-Molina L, Margueron R, Fleury-Olela F, Conquet F, Schibler U, Bonfils C (1999) Circadian expression of the steroid 15 alpha-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor DBP. Mol Cell Biol 19:6488–6499PubMedGoogle Scholar
  65. Lee C, Etchegaray JP, Cagampang FR, Loudon AS, Reppert SM (2001) Posttranslational mechanisms regulate the mammalian circadian clock. Cell 107:855–867PubMedCrossRefGoogle Scholar
  66. Lemberger T, Saladin R, Vazquez M, Assimacopoulos F, Staels B, Desvergne B, Wahli W, Auwerx J (1996) Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm. J Biol Chem 271:1764–1769PubMedCrossRefGoogle Scholar
  67. Lemmer B (1995) Clinical chronopharmacology: the importance of time in drug treatment. Ciba Found Symp 183:235–247; discussion 247–253Google Scholar
  68. Lemmer B, Nold G, Behne S, Kaiser R (1991) Chronopharmacokinetics and cardiovascular effects of nifedipine. Chronobiol Int 8:485–494PubMedCrossRefGoogle Scholar
  69. LeSauter J, Hoque N, Weintraub M, Pfaff DW, Silver R (2009) Stomach ghrelin-secreting cells as food-entrainable circadian clocks. Proc Natl Acad Sci USA 106:13582–13587PubMedCrossRefGoogle Scholar
  70. Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, Ivanova G, Omura C, Mo S, Vitaterna MH, Lopez JP, Philipson LH, Bradfield CA, Crosby SD, JeBailey L, Wang X, Takahashi JS, Bass J (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466:627–631PubMedCrossRefGoogle Scholar
  71. Marcheva B, Ramsey KM, Peek CB, Affinati A, Maury E, Bass J (2013) Circadian clocks and metabolism. In: Kramer A, Merrow M (eds) Circadian clocks, vol 127, Handbook of experimental pharmacology. Springer, HeidelbergGoogle Scholar
  72. Minors D, Waterhouse J, Hume K, Marks M, Arendt J, Folkard S, Akerstedt T (1988) Sleep and circadian rhythms of temperature and urinary excretion on a 22.8 hr “day”. Chronobiol Int 5: 65–80PubMedCrossRefGoogle Scholar
  73. Moore JG, Englert E Jr (1970) Circadian rhythm of gastric acid secretion in man. Nature 226: 1261–1262PubMedCrossRefGoogle Scholar
  74. Muller FO, Van Dyk M, Hundt HK, Joubert AL, Luus HG, Groenewoud G, Dunbar GC (1987) Pharmacokinetics of temazepam after day-time and night-time oral administration. Eur J Clin Pharmacol 33:211–214PubMedCrossRefGoogle Scholar
  75. Murakami Y, Higashi Y, Matsunaga N, Koyanagi S, Ohdo S (2008) Circadian clock-controlled intestinal expression of the multidrug-resistance gene mdr1a in mice. Gastroenterology 135(1636–1644): e3PubMedGoogle Scholar
  76. Nader N, Chrousos GP, Kino T (2009) Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J 23:1572–1583PubMedCrossRefGoogle Scholar
  77. Nair V, Casper R (1969) The influence of light on daily rhythm in hepatic drug metabolizing enzymes in rat. Life Sci 8:1291–1298PubMedCrossRefGoogle Scholar
  78. Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, Guarente LP, Sassone-Corsi P (2008) The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329–340PubMedCrossRefGoogle Scholar
  79. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324:654–657PubMedCrossRefGoogle Scholar
  80. Nakamura TJ, Nakamura W, Yamazaki S, Kudo T, Cutler T, Colwell CS, Block GD (2011) Age-related decline in circadian output. J Neurosci 31:10201–10205PubMedCrossRefGoogle Scholar
  81. Nakano S, Hollister LE (1983) Chronopharmacology of amitriptyline. Clin Pharmacol Ther 33: 453–459PubMedCrossRefGoogle Scholar
  82. Nakano S, Watanabe H, Nagai K, Ogawa N (1984) Circadian stage-dependent changes in diazepam kinetics. Clin Pharmacol Ther 36:271–277PubMedCrossRefGoogle Scholar
  83. Oishi K, Shirai H, Ishida N (2005) CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPAR alpha) in mice. Biochem J 386:575–581PubMedCrossRefGoogle Scholar
  84. Ortiz-Tudela E, Mteyrek A, Ballesta A, Innominato PF, Lévi F (2013) Cancer chronotherapeutics: experimental, theoretical and clinical aspects. In: Kramer A, Merrow M (eds) Circadian clocks, vol 127, Handbook of experimental pharmacology. Springer, HeidelbergGoogle Scholar
  85. Pan X, Hussain MM (2007) Diurnal regulation of microsomal triglyceride transfer protein and plasma lipid levels. J Biol Chem 282:24707–24719PubMedCrossRefGoogle Scholar
  86. Pan X, Hussain MM (2009) Clock is important for food and circadian regulation of macronutrient absorption in mice. J Lipid Res 50:1800–1813PubMedCrossRefGoogle Scholar
  87. Pan X, Zhang Y, Wang L, Hussain MM (2010) Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP. Cell Metab 12:174–186PubMedCrossRefGoogle Scholar
  88. Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109:307–320PubMedCrossRefGoogle Scholar
  89. Paschos GK, FitzGerald GA (2010) Circadian clocks and vascular function. Circ Res 106:833–841PubMedCrossRefGoogle Scholar
  90. Paschos GK, Baggs JE, Hogenesch JB, FitzGerald GA (2010) The role of clock genes in pharmacology. Annu Rev Pharmacol Toxicol 50:187–214PubMedCrossRefGoogle Scholar
  91. Patel IH, Venkataramanan R, Levy RH, Viswanathan CT, Ojemann LM (1982) Diurnal oscillations in plasma protein binding of valproic acid. Epilepsia 23:283–290PubMedCrossRefGoogle Scholar
  92. Perry EK, Perry RH, Taylor MJ, Tomlinson BE (1977a) Circadian variation in human brain enzymes. Lancet 1:753–754PubMedCrossRefGoogle Scholar
  93. Perry EK, Perry RH, Taylor MJ, Tomlinson BE (1977b) Evidence of a circadian fluctuation in neurotransmitter enzyme activities measured in autopsy human brain. J Neurochem 29: 593–594PubMedCrossRefGoogle Scholar
  94. Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U (2002) The orphan nuclear receptor REV-ERB alpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110:251–260PubMedCrossRefGoogle Scholar
  95. Ptitsyn AA, Zvonic S, Conrad SA, Scott LK, Mynatt RL, Gimble JM (2006) Circadian clocks are resounding in peripheral tissues. PLoS Comput Biol 2:e16PubMedCrossRefGoogle Scholar
  96. Qu X, Metz RP, Porter WW, Neuendorff N, Earnest BJ, Earnest DJ (2010) The clock genes period 1 and period 2 mediate diurnal rhythms in dioxin-induced Cyp1A1 expression in the mouse mammary gland and liver. Toxicol Lett 196:28–32PubMedCrossRefGoogle Scholar
  97. Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C, Takahashi JS, Imai S, Bass J (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324:651–654PubMedCrossRefGoogle Scholar
  98. Reick M, Garcia JA, Dudley C, McKnight SL (2001) NPAS2: an analog of clock operative in the mammalian forebrain. Science 293:506–509PubMedCrossRefGoogle Scholar
  99. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418: 935–941PubMedCrossRefGoogle Scholar
  100. Riva R, Albani F, Ambrosetto G, Contin M, Cortelli P, Perucca E, Baruzzi A (1984) Diurnal fluctuations in free and total steady-state plasma levels of carbamazepine and correlation with intermittent side effects. Epilepsia 25:476–481PubMedCrossRefGoogle Scholar
  101. Rutter J, Reick M, Wu LC, McKnight SL (2001) Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293:510–514PubMedCrossRefGoogle Scholar
  102. Sahar S, Sassone-Corsi P (2013) The epigenetic language of circadian clocks. In: Kramer A, Merrow M (eds) Circadian clocks, vol 127, Handbook of experimental pharmacology. Springer, HeidelbergGoogle Scholar
  103. Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA, FitzGerald GA, Kay SA, Hogenesch JB (2004) A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 43:527–537PubMedCrossRefGoogle Scholar
  104. Scheidel B, Lemmer B (1991) Chronopharmacology of oral nitrates in healthy subjects. Chronobiol Int 8:409–419PubMedCrossRefGoogle Scholar
  105. Scheving LA (2000) Biological clocks and the digestive system. Gastroenterology 119:536–549PubMedCrossRefGoogle Scholar
  106. Scheving LA, Russell WE (2007) It’s about time: clock genes unveiled in the gut. Gastroenterology 133:1373–1376PubMedCrossRefGoogle Scholar
  107. Scheving LE, Pauly JE, Tsai TH (1968) Circadian fluctuation in plasma proteins of the rat. Am J Physiol 215:1096–1101PubMedGoogle Scholar
  108. Shiga T, Fujimura A, Tateishi T, Ohashi K, Ebihara A (1993) Differences of chronopharmacokinetic profiles between propranolol and atenolol in hypertensive subjects. J Clin Pharmacol 33:756–761PubMedCrossRefGoogle Scholar
  109. Shimba S, Watabe Y (2009) Crosstalk between the AHR signaling pathway and circadian rhythm. Biochem Pharmacol 77:560–565PubMedCrossRefGoogle Scholar
  110. Slat E, Freeman GM, Herzog ED (2013) The clock in the brain: neurons, glia and networks in daily rhythms. In: Kramer A, Merrow M (eds) Circadian clocks, vol 127, Handbook of experimental pharmacology. Springer, HeidelbergGoogle Scholar
  111. Snyder SH, Zweig M, Axelrod J, Fischer JE (1965) Control of the circadian rhythm in serotonin content of the rat pineal gland. Proc Natl Acad Sci USA 53:301–305PubMedCrossRefGoogle Scholar
  112. Snyder SH, Axelrod J, Zweig M (1967) Circadian rhythm in the serotonin content of the rat pineal gland: regulating factors. J Pharmacol Exp Ther 158:206–213PubMedGoogle Scholar
  113. Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo SH, Takahashi JS, Butler AA, Kamenecka TM, Burris TP (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 485:62–68PubMedCrossRefGoogle Scholar
  114. Sprouse J, Braselton J, Reynolds L (2006) Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. Biol Psychiatry 60:896–899PubMedCrossRefGoogle Scholar
  115. Stearns AT, Balakrishnan A, Rhoads DB, Ashley SW, Tavakkolizadeh A (2008) Diurnal rhythmicity in the transcription of jejunal drug transporters. J Pharmacol Sci 108:144–148PubMedCrossRefGoogle Scholar
  116. Stow LR, Gumz ML (2010) The circadian clock in the kidney. J Am Soc Nephrol 22:598–604CrossRefGoogle Scholar
  117. Sukumaran S, Almon RR, DuBois DC, Jusko WJ (2010) Circadian rhythms in gene expression: relationship to physiology, disease, drug disposition and drug action. Adv Drug Deliv Rev 62: 904–917PubMedCrossRefGoogle Scholar
  118. Sun X, Deng J, Liu T, Borjigin J (2002) Circadian 5-HT production regulated by adrenergic signaling. Proc Natl Acad Sci USA 99:4686–4691PubMedCrossRefGoogle Scholar
  119. Takahashi S, Inoue I, Nakajima Y, Seo M, Nakano T, Yang F, Kumagai M, Komoda T, Awata T, Ikeda M, Katayama S (2010) A promoter in the novel exon of hPPAR gamma directs the circadian expression of PPAR gamma. J Atheroscler Thromb 17:73–83PubMedCrossRefGoogle Scholar
  120. Tanimura N, Kusunose N, Matsunaga N, Koyanagi S, Ohdo S (2011) Aryl hydrocarbon receptor-mediated Cyp1a1 expression is modulated in a CLOCK-dependent circadian manner. Toxicology 290(2–3):203–207PubMedCrossRefGoogle Scholar
  121. Taylor DR, Duffin D, Kinney CD, McDevitt DG (1983) Investigation of diurnal changes in the disposition of theophylline. Br J Clin Pharmacol 16:413–416PubMedCrossRefGoogle Scholar
  122. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR, Eckel RH, Takahashi JS, Bass J (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308:1043–1045PubMedCrossRefGoogle Scholar
  123. Uz T, Ahmed R, Akhisaroglu M, Kurtuncu M, Imbesi M, Dirim Arslan A, Manev H (2005) Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum. Neuroscience 134:1309–1316PubMedCrossRefGoogle Scholar
  124. Wang N, Yang G, Jia Z, Zhang H, Aoyagi T, Soodvilai S, Symons JD, Schnermann JB, Gonzalez FJ, Litwin SE, Yang T (2008) Vascular PPAR gamma controls circadian variation in blood pressure and heart rate through Bmal1. Cell Metab 8:482–491PubMedCrossRefGoogle Scholar
  125. Weinert H, Weinert D, Schurov I, Maywood ES, Hastings MH (2001) Impaired expression of the mPer2 circadian clock gene in the suprachiasmatic nuclei of aging mice. Chronobiol Int 18: 559–565PubMedCrossRefGoogle Scholar
  126. Wilkinson GR, Beckett AH (1968) Absorption metabolism and excretion of the ephedrines in man. I. The influence of urinary pH and urine volume output. J Pharmacol Exp Ther 162:139–147PubMedGoogle Scholar
  127. Wirz-Justice A (1987) Circadian rhythms in mammalian neurotransmitter receptors. Prog Neurobiol 29:219–259PubMedCrossRefGoogle Scholar
  128. Xu CX, Krager SL, Liao DF, Tischkau SA (2010) Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene. Toxicol Sci 115:98–108PubMedCrossRefGoogle Scholar
  129. Yuan Q, Lin F, Zheng X, Sehgal A (2005) Serotonin modulates circadian entrainment in Drosophila. Neuron 47:115–127PubMedCrossRefGoogle Scholar
  130. Yujnovsky I, Hirayama J, Doi M, Borrelli E, Sassone-Corsi P (2006) Signaling mediated by the dopamine D2 receptor potentiates circadian regulation by CLOCK:BMAL1. Proc Natl Acad Sci USA 103:6386–6391PubMedCrossRefGoogle Scholar
  131. Zhang YK, Yeager RL, Klaassen CD (2009) Circadian expression profiles of drug-processing genes and transcription factors in mouse liver. Drug Metab Dispos 37:106–115PubMedCrossRefGoogle Scholar
  132. Zhang EE, Liu Y, Dentin R, Pongsawakul PY, Liu AC, Hirota T, Nusinow DA, Sun X, Landais S, Kodama Y, Brenner DA, Montminy M, Kay SA (2011) Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med 16:1152–1156CrossRefGoogle Scholar
  133. Zheng X, Yang Z, Yue Z, Alvarez JD, Sehgal A (2007) FOXO and insulin signaling regulate sensitivity of the circadian clock to oxidative stress. Proc Natl Acad Sci USA 104: 15899–15904PubMedCrossRefGoogle Scholar
  134. Zhou YD, Barnard M, Tian H, Li X, Ring HZ, Francke U, Shelton J, Richardson J, Russell DW, McKnight SL (1997) Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system. Proc Natl Acad Sci USA 94: 713–718PubMedCrossRefGoogle Scholar
  135. Zuber AM, Centeno G, Pradervand S, Nikolaeva S, Maquelin L, Cardinaux L, Bonny O, Firsov D (2009) Molecular clock is involved in predictive circadian adjustment of renal function. Proc Natl Acad Sci USA 106:16523–16528PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of NeurologyWashington University School of MedicineSaint LouisUSA
  2. 2.Department of Pharmacology, Institute for Translational Medicine and Therapeutics, 10-122 Translational Research CenterUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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