caa a22 4500 606235035 CHVBK 20210128101240.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2219-8 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2219-8 Acute inhibition of casein kinase 1δ/ε rapidly delays peripheral clock gene rhythms [Elektronische Daten] [D. Kennaway, T. Varcoe, A. Voultsios, M. Salkeld, L. Rattanatray, M. Boden] Circadian rhythms are generated through a transcription-translation feedback loop involving clock genes and the casein kinases CSNK1D and CSNK1E. In this study, we investigated the effects of the casein kinase inhibitor PF-670462 (50mg/kg) on rhythmic expression of clock genes in the liver, pancreas and suprachiasmatic nucleus (SCN) as well as plasma corticosterone, melatonin and running behaviour in rats and compared them to the responses to a 4h extension of the light phase. PF-670462 acutely phase delayed the rhythmic transcription of Bmal1, Per1, Per2 and Nr1d1 in both liver and pancreas by 4.5±1.3 and 4.5±1.2h, respectively, 1day after administration. In the SCN, the rhythm of Nr1d1 and Dbp mRNA expression was delayed by 4.2 and 4h, respectively. Despite these changes, the time of peak plasma melatonin secretion was not delayed, although the plasma corticosterone rhythm and onset of wheel-running activity were delayed by 2.1 and 1.1h, respectively. These changes are in contrast to the effects of the 4h light extension, which resulted in delays in peak expression of the clock genes of less than 1h and no change in the melatonin or corticosterone rhythms. The ability of the casein kinase inhibitor to bring about large phase shifts in the rhythms of major metabolic target tissues may lead to new drugs being developed to rapidly phase adjust circadian rhythms to alleviate the metabolic impact of shift work. Springer Science+Business Media New York, 2014 Circadian nationallicence Transcription factors nationallicence Suprachiasmatic nucleus nationallicence Melatonin nationallicence Corticosterone nationallicence Actb : Beta actin nationallicence Bmal1 : Brain and muscle ARNT-like protein 1, Arntl and Mop3 nationallicence Nr1d1 : Nuclear receptor subfamily 1, group D, member 1, also known as Rev erb alpha nationallicence Per1 : Period 1 nationallicence Per2 : Period 2 nationallicence Cry1 : Cryptochrome 1 nationallicence Cry2 : Cryptochrome 2 nationallicence Dbp : D site of albumin promoter (albumin D-box) binding protein nationallicence Kennaway D. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut Varcoe T. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut Voultsios A. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut Salkeld M. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut Rattanatray L. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut Boden M. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 195-206 0300-8177 398:1-2<195 2015 398 11010 https://doi.org/10.1007/s11010-014-2219-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2219-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kennaway D. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Varcoe T. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Voultsios A. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Salkeld M. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Rattanatray L. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Boden M. Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, 5005, Adelaide, SA, Australia aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 195-206 0300-8177 398:1-2<195 2015 398 11010