Pituitary adenylate cyclase-activating polypeptide (PACAP) can act as determinant of the tyrosine hydroxylase phenotype of dopaminergic cells during retina development

Autor: Juliana Carrazzoni Borba, Isabela Pereira Henze, Mariana S. Silveira, Patrícia F. Gardino, Regina Célia Cussa Kubrusly, Fernando G. de Mello, Maria Christina Fialho de Mello, Jan Nora Hokoç
Rok vydání: 2005
Předmět:
Time Factors
IBMX
Tyrosine 3-Monooxygenase
Phosphodiesterase Inhibitors
Dopamine
Blotting
Western
Cell Culture Techniques
Receptors
Pituitary Adenylate Cyclase-Activating Polypeptide
8-Bromo Cyclic Adenosine Monophosphate
Cell Count
Receptors
Cell Surface
Chick Embryo
Biology
Retina
chemistry.chemical_compound
Developmental Neuroscience
1-Methyl-3-isobutylxanthine
Dopaminergic Cell
Cyclic AMP
medicine
Animals
Drug Interactions
Nerve Growth Factors
RNA
Messenger
Tyrosine
Neurons
Neurotransmitter Agents
Microscopy
Confocal
Forskolin
Dose-Response Relationship
Drug
Tyrosine hydroxylase
Reverse Transcriptase Polymerase Chain Reaction
Colforsin
Neuropeptides
Age Factors
Immunohistochemistry
Molecular biology
Phenotype
medicine.anatomical_structure
Animals
Newborn
Gene Expression Regulation
chemistry
Inner nuclear layer
Catecholamine
Pituitary Adenylate Cyclase-Activating Polypeptide
Receptors
Pituitary Adenylate Cyclase-Activating Polypeptide
Type I
Developmental Biology
medicine.drug
Zdroj: Developmental Brain Research. 156:193-201
ISSN: 0165-3806
DOI: 10.1016/j.devbrainres.2005.02.016
Popis: In the chick retina, dopaminergic cells are generated between embryonic days 3 and 7 (E3/E7). However, the expression of tyrosine hydroxylase (TH), the first enzyme in the catecholamine synthetic pathway, is only detected after E11/E12. During the interval comprising E7 to E12, signals conveyed by cAMP are important to determine the TH phenotype. The present study shows that pituitary adenylyl cyclase-activating polypeptide (PACAP), via cAMP, is a major endogenous component in defining the TH phenotype of retina dopaminergic cells during development. PACAP type 1 receptor and its mRNA were detected in retinas since E6. PACAP was also immunodetected in cells localized in the inner nuclear layer of retinas since E8. This peptide promoted greater than 10-fold increase in cAMP accumulation of retinas obtained from embryos since E8, an effect that was blocked by PACAP6-38 (PAC1 receptor antagonist). In cultured retina cells from E8 and E9, maintained for 6 days in vitro with 10 nM PACAP (for 5 days), the number of dopaminergic cells expressing tyrosine hydroxylase increased 2.4-fold. The cAMP analog, 8-Br-cAMP and 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor) also increased the number of tyrosine hydroxylase-positive cells by 4- to 6-fold. IBMX plus PACAP treatment resulted in 17-fold increase in the number of cells positive for tyrosine hydroxylase. Under this condition the amount of tyrosine hydroxylase expression, as detected by western blot analysis, was also increased. The protein kinase-A inhibitor, rp-cAMPS, significantly reduced the effect of PACAP. Our data show that this peptide is an important factor influencing the definition of the tyrosine hydroxylase phenotype of retina dopaminergic cells within a narrow window of development.
Databáze: OpenAIRE
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