PMID- 18670077
OWN - NLM
STAT- MEDLINE
DCOM- 20080930
LR  - 20221207
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 31
IP  - 8
DP  - 2008 Aug
TI  - Some selective serotonin reuptake inhibitors inhibit dynamin I guanosine 
      triphosphatase (GTPase).
PG  - 1489-95
AB  - Neuronal dynamin I plays a critical role in the recycling of synaptic vesicles, 
      and thus in nervous system function. We expressed and purified dynamin I to 
      explore potentially clinically useful endocytosis inhibitors and to examine the 
      mechanism of their action. We estimated the IC(50) of nineteen psychotropic drugs 
      for dynamin I. The IC(50) values of two selective serotonin reuptake inhibitors 
      (sertraline and fluvoxamine) were 7.3+/-1.0 and 14.7+/-1.6 microM, respectively. 
      Kinetic analyses revealed that fluvoxamine is a noncompetitive inhibitor of 
      dynamin I guanosine triphosphatase (GTPase) with respect to guanosine 
      5'-triphosphate (GTP) and a competitive inhibitor with respect to 
      L-phosphatidylserine (PS). Fluvoxamine may compete with PS for binding to the 
      pleckstrin homology domain of dynamin I. On the other hand, sertraline was a 
      mixed type inhibitor with respect to both GTP and PS. Our results indicate that 
      sertraline and fluvoxamine may regulate the transportation of neurotransmitters 
      by modulating synaptic vesicle endocytosis via the inhibition of dynamin I 
      GTPase.
FAU - Otomo, Masahiro
AU  - Otomo M
AD  - Department of Neuropsychiatry, St. Marianna University School of Medicine, 
      Kanagawa, Japan.
FAU - Takahashi, Kiyofumi
AU  - Takahashi K
FAU - Miyoshi, Hiroshi
AU  - Miyoshi H
FAU - Osada, Kenichi
AU  - Osada K
FAU - Nakashima, Hideki
AU  - Nakashima H
FAU - Yamaguchi, Noboru
AU  - Yamaguchi N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - EC 3.5.1.50 (Dynamin I)
RN  - O4L1XPO44W (Fluvoxamine)
RN  - QUC7NX6WMB (Sertraline)
SB  - IM
MH  - Animals
MH  - Dynamin I/*antagonists & inhibitors/genetics
MH  - Endocytosis/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Escherichia coli/genetics
MH  - Fluvoxamine/pharmacology
MH  - Genetic Vectors
MH  - Kinetics
MH  - Mice
MH  - Plasmids/genetics
MH  - Psychotropic Drugs/pharmacology
MH  - *Selective Serotonin Reuptake Inhibitors
MH  - Sertraline/pharmacology
EDAT- 2008/08/02 09:00
MHDA- 2008/10/01 09:00
CRDT- 2008/08/02 09:00
PHST- 2008/08/02 09:00 [pubmed]
PHST- 2008/10/01 09:00 [medline]
PHST- 2008/08/02 09:00 [entrez]
AID - JST.JSTAGE/bpb/31.1489 [pii]
AID - 10.1248/bpb.31.1489 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2008 Aug;31(8):1489-95. doi: 10.1248/bpb.31.1489.