PMID- 11867712
OWN - NLM
STAT- MEDLINE
DCOM- 20020426
LR  - 20221101
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 99
IP  - 5
DP  - 2002 Mar 5
TI  - Nitric oxide down-regulates brain-derived neurotrophic factor secretion in 
      cultured hippocampal neurons.
PG  - 3282-7
AB  - The regulation of neurotrophin (NT) secretion is critical for many aspects of 
      NT-mediated neuronal plasticity. Neurons release NTs by activity-regulated 
      secretion pathways, initiated either by neurotransmitters and/or by existing NTs 
      by a positive-feedback mechanism. This process depends on calcium release from 
      intracellular stores. Little is known, however, about potential pathways that 
      down-regulate NT secretion. Here we demonstrate that nitric oxide (NO) induces a 
      rapid down-regulation of brain-derived neurotrophic factor (BDNF) secretion in 
      cultured hippocampal neurons. Similar effects occur by activating a downstream 
      target of intracellular NO, the soluble guanylyl cyclase, or by increasing the 
      levels of its product, cGMP. Furthermore, down-regulation of BDNF secretion is 
      mediated by cGMP-activated protein kinase G, which prevents calcium release from 
      inositol 1,4,5-trisphosphate-sensitive stores. Our data indicate that the 
      NO/cGMP/protein kinase G pathway represents a signaling mechanism by which 
      neurons can rapidly down-regulate BDNF secretion and suggest that, in hippocampal 
      neurons, NT secretion is finely tuned by both stimulatory and inhibitory signals.
FAU - Canossa, Marco
AU  - Canossa M
AD  - Department of Pharmacology, University of Bologna, via Irnerio 48, 40216 Bologna, 
      Italy. marco@biofarm.unibo.it
FAU - Giordano, Emanuele
AU  - Giordano E
FAU - Cappello, Silvia
AU  - Cappello S
FAU - Guarnieri, Carlo
AU  - Guarnieri C
FAU - Ferri, Sergio
AU  - Ferri S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020226
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Nitro Compounds)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 92454-60-9 (FK 409)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Cyclic GMP/metabolism
MH  - Cyclic GMP-Dependent Protein Kinases/metabolism
MH  - *Down-Regulation
MH  - Hippocampus/cytology/metabolism
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/pharmacology
MH  - Nitro Compounds/pharmacology
MH  - Nitroprusside/pharmacology
MH  - Rats
PMC - PMC122510
EDAT- 2002/02/28 10:00
MHDA- 2002/04/27 10:01
PMCR- 2002/09/05
CRDT- 2002/02/28 10:00
PHST- 2002/02/28 10:00 [pubmed]
PHST- 2002/04/27 10:01 [medline]
PHST- 2002/02/28 10:00 [entrez]
PHST- 2002/09/05 00:00 [pmc-release]
AID - 042504299 [pii]
AID - 5042 [pii]
AID - 10.1073/pnas.042504299 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3282-7. doi: 10.1073/pnas.042504299. 
      Epub 2002 Feb 26.