Phosphodiesterase type 2 and the homeostasis of cyclic GMP in living thalamic neurons

Autor: Hepp, R., Tricoire, L., Hu, E., Gervasi, N., Paupardin-Tritsch, D., Lambolez, B., Vincent, P.
Přispěvatelé: Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2007
Předmět:
MESH: Signal Transduction
Patch-Clamp Techniques
MESH: Fluorescence Resonance Energy Transfer
Phosphodiesterase Inhibitors
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
MESH: Neurons
MESH: Nitric Oxide Synthase Type I
MESH: Carrier Proteins
Nitric Oxide Synthase Type I
Nitric Oxide
MESH: Phosphodiesterase Inhibitors
Mice
Organ Culture Techniques
Thalamus
MESH: Mice
Inbred C57BL
1-Methyl-3-isobutylxanthine
MESH: Patch-Clamp Techniques
Fluorescence Resonance Energy Transfer
MESH: Cyclic GMP
Animals
Homeostasis
MESH: Animals
Nitric Oxide Donors
MESH: Mice
Cyclic GMP
Fluorescent Dyes
MESH: Thalamus
Neurons
Phosphoric Diester Hydrolases
MESH: 1-Methyl-3-isobutylxanthine
MESH: Nitric Oxide Donors
MESH: Fluorescent Dyes
Cyclic Nucleotide Phosphodiesterases
Type 2
MESH: Organ Culture Techniques
Mice
Inbred C57BL
MESH: Homeostasis
MESH: Nitric Oxide
Carrier Proteins
MESH: Phosphoric Diester Hydrolases
Signal Transduction
Zdroj: Journal of Neurochemistry
Journal of Neurochemistry, 2007, 102 (6), pp.1875-86. ⟨10.1111/j.1471-4159.2007.04657.x⟩
Journal of Neurochemistry, Wiley, 2007, 102 (6), pp.1875-86. ⟨10.1111/j.1471-4159.2007.04657.x⟩
ISSN: 0022-3042
1471-4159
DOI: 10.1111/j.1471-4159.2007.04657.x⟩
Popis: The ubiquitous second messenger cyclic GMP (cGMP) is synthesized by soluble guanylate cyclases in response to nitric oxide (NO) and degraded by phosphodiesterases (PDE). We studied the homeostasis of cGMP in living thalamic neurons by using the genetically encoded fluorescence resonance energy transfer sensor Cygnet, expressed in brain slices through viral gene transfer. Natriuretic peptides had no effect on cGMP. Basal cGMP levels decreased upon inhibition of NO synthases or soluble guanylate cyclases and increased when PDEs were inhibited. Single cell RT-PCR analysis showed that thalamic neurons express PDE1, PDE2, PDE9, and PDE10. Basal cGMP levels were increased by the PDE2 inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and BAY60-7550 but were unaffected by PDE1 or PDE10 inhibitors. We conclude that PDE2 regulates the basal cGMP concentration in thalamic neurons. In addition, in the presence of 3-isobutyl-1-methylxanthine (IBMX), cGMP still decreased after application of a NO donor. Probenecid, a blocker of cGMP transporters, had no effect on this decrease, leaving PDE9 as a possible candidate for decreasing cGMP concentration. Basal cGMP level is poised at an intermediate level from which it can be up or down-regulated according to the cyclase and PDE activities.
Databáze: OpenAIRE
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