PMID- 11709199
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 62
IP  - 10
DP  - 2001 Nov 15
TI  - Up-regulation by clarithromycin of alpha(1)-acid glycoprotein expression in liver 
      and primary cultured hepatocytes.
PG  - 1391-7
AB  - alpha(1)-Acid glycoprotein (AGP) is the major transport protein for cationic 
      drugs, endogenous ligands, and some anionic drugs in plasma. Hepatic synthesis 
      and secretion of AGP are altered during acute inflammation as well as by a number 
      of drugs. This alteration could influence the binding of drugs and its biological 
      function. Macrolide antibiotics are widely used in the treatment of a variety of 
      infectious diseases. The effects of macrolide antibiotics have been studied with 
      respect to rat AGP expression in vivo. After the individual administration of six 
      macrolides to rats, with the exception of oleandomycin, five increased AGP levels 
      in serum. Of these five, clarithromycin (CAM) was the most potent inducer of AGP, 
      which reached a maximum level between 3 to 7 days after administration. CAM 
      increased the steady-state level of AGP mRNA in liver as well as protein level in 
      serum in a dose-dependent manner. In addition, CAM increased AGP mRNA levels in 
      primary cultured hepatocytes. In the luciferase promoter assay, CAM potentiated 
      dexamethasone-increased promoter activity of the AGP gene, which contained the 
      glucocorticoid response element, in cultured rat hepatocytes, although CAM itself 
      had no effect on its activity. The effect of CAM and dexamethasone was diminished 
      by glucocorticoid response element deletion or mutation or by adding the 
      antiglucocorticoid, RU486. Further, in the mouse mammary tumor virus (MMTV) 
      promoter containing functional glucocorticoid response element, CAM potentiated 
      dexamethasone-increased promoter activity. In the adrenalectomized rats, CAM did 
      not increase AGP levels in serum. These findings suggest that CAM may cause 
      transcriptional induction of AGP, at least in part, via a glucocorticoid-mediated 
      mechanism.
FAU - Komori, T
AU  - Komori T
AD  - Faculty of Pharmaceutical Sciences, Kumamoto University, 862-0973, Kumamoto, 
      Japan.
FAU - Kai, H
AU  - Kai H
FAU - Shimoishi, K
AU  - Shimoishi K
FAU - Kabu, K
AU  - Kabu K
FAU - Nonaka, A
AU  - Nonaka A
FAU - Maruyama, T
AU  - Maruyama T
FAU - Tamura, K
AU  - Tamura K
FAU - Otagiri, M
AU  - Otagiri M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Glucocorticoids)
RN  - 0 (Orosomucoid)
RN  - 0 (RNA, Messenger)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - H1250JIK0A (Clarithromycin)
SB  - IM
MH  - 5' Untranslated Regions/drug effects/genetics
MH  - Adrenalectomy
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Cells, Cultured
MH  - Clarithromycin/*pharmacology
MH  - Dexamethasone/pharmacology
MH  - Drug Interactions
MH  - Gene Expression/drug effects
MH  - Glucocorticoids/physiology
MH  - Hepatocytes/drug effects/metabolism
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - Orosomucoid/genetics/*metabolism
MH  - RNA Stability/drug effects
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Up-Regulation/drug effects
EDAT- 2001/11/16 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/16 10:00
PHST- 2001/11/16 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/16 10:00 [entrez]
AID - S0006-2952(01)00778-X [pii]
AID - 10.1016/s0006-2952(01)00778-x [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2001 Nov 15;62(10):1391-7. doi: 10.1016/s0006-2952(01)00778-x.