PMID- 9307328
OWN - NLM
STAT- MEDLINE
DCOM- 19971218
LR  - 20190725
IS  - 0021-5198 (Print)
IS  - 0021-5198 (Linking)
VI  - 74
IP  - 4
DP  - 1997 Aug
TI  - Inhibitory mechanism of mizoribine on the antibody production of mouse B cells 
      stimulated with lipopolysaccharide.
PG  - 323-30
AB  - It has been reported that the immunosuppressant mizoribine (MZR) inhibits T cell 
      proliferation by depleting intracellular guanine nucleotides via competitive 
      inhibition of inosine 5'-monophosphate (IMP) dehydrogenase in the purine 
      metabolism pathway. This study was performed to determine if the mechanism by 
      which MZR suppresses the proliferation of mouse B cells and antibody production 
      by these cells is dependent on the depletion of intracellular guanine 
      nucleotides. Stimulation of purified splenic B cells of mice with 
      lipopolysaccharide (LPS), a mitogen to B cells, increased both proliferation and 
      antibody production. MZR suppressed both of these functions in a dose-dependent 
      fashion. MZR also caused a decrease in the amount of intracellular guanosine 
      5'-triphosphate (GTP). When the cultures were grown on plates containing 
      guanosine plus 8-aminoguanosine, the amount of intracellular GTP, which had been 
      reduced by MZR, was restored. Furthermore, the repletion of GTP pools restored 
      both proliferation and antibody production almost to their previous levels. These 
      results suggest that MZR suppresses antibody production and proliferation of B 
      cells by acting directly on B cells. Furthermore, it is suggested that the 
      inhibitory effect of MZR on antibody production, as well as on T cell 
      proliferation, is dependent on the decrease in intracellular guanine nucleotide 
      pools of mouse B cells.
FAU - Kamada, H
AU  - Kamada H
AD  - Laboratory for Immunology, Institute for Life Science Research, Asahi Chemical 
      Industry Co., Ltd., Shizuoka, Japan.
FAU - Itoh, H
AU  - Itoh H
FAU - Shibata, H
AU  - Shibata H
FAU - Koshio, T
AU  - Koshio T
FAU - Hayashi, A
AU  - Hayashi A
FAU - Nakagami, K
AU  - Nakagami K
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Jpn J Pharmacol
JT  - Japanese journal of pharmacology
JID - 2983305R
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Ribonucleosides)
RN  - 12133JR80S (Guanosine)
RN  - 3868-32-4 (8-aminoguanosine)
RN  - 4JR41A10VP (mizoribine)
RN  - 86-01-1 (Guanosine Triphosphate)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Antibody Formation/*drug effects/immunology
MH  - Antibody Specificity/drug effects/immunology
MH  - B-Lymphocytes/*drug effects/*immunology
MH  - Cell Division/drug effects/immunology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Guanosine/analogs & derivatives/pharmacology
MH  - Guanosine Triphosphate/*metabolism
MH  - Immunosuppressive Agents/*pharmacology
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Ribonucleosides/*pharmacology
MH  - Spleen/cytology/drug effects/immunology
EDAT- 1997/08/01 00:00
MHDA- 1997/11/05 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/11/05 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
AID - 10.1254/jjp.74.323 [doi]
PST - ppublish
SO  - Jpn J Pharmacol. 1997 Aug;74(4):323-30. doi: 10.1254/jjp.74.323.