Neuropeptide Y stimulates retinal neural cell proliferation--involvement of nitric oxide.
Neuropeptide Y (NPY) is a 36 amino acid peptide widely present in the CNS, including the retina. Previous studies have demonstrated that NPY promotes cell proliferation of rat post-natal hippocampal and olfactory epithelium precursor cells. The aim of this work was to investigate the role of NPY on cell proliferation of rat retinal neural cells. For this purpose, primary retinal cell cultures expressing NPY, and NPY Y(1), Y(2), Y(4) and Y(5) receptors [Alvaro et al., (2007) Neurochem. Int., 50, 757] were used. NPY (10-1000 nM) stimulated cell proliferation through the activation of NPY Y(1), Y(2) and Y(5) receptors. NPY also increased the number of proliferating neuronal progenitor cells (BrdU(+)/nestin(+) cells). The intracellular mechanisms coupled to NPY receptors activation that mediate the increase in cell proliferation were also investigated. The stimulatory effect of NPY on cell proliferation was reduced by L-nitroarginine-methyl-esther (L-NAME; 500 microM), a nitric oxide synthase inhibitor, 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ; 20 microM), a soluble guanylyl cyclase inhibitor or U0126 (1 microM), an inhibitor of the extracellular signal-regulated kinase 1/2 (ERK 1/2). In conclusion, NPY stimulates retinal neural cell proliferation, and this effect is mediated through nitric oxide-cyclic GMP and ERK 1/2 pathways.
Alvaro
Ana Rita
AR
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Martins
João
J
Araújo
Inês M
IM
Rosmaninho-Salgado
Joana
J
Ambrósio
António F
AF
Cavadas
Cláudia
C
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology; D048370:MAP Kinase Kinase 2 / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009478:Neuropeptide Y / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D009478:Neuropeptide Y; D009569:Nitric Oxide; D048052:Mitogen-Activated Protein Kinase 3; D048370:MAP Kinase Kinase 2; D006152:Cyclic GMP