Effect of ATP on astrocyte stellation is switched from suppressive to stimulatory during development.
Adenosine 5'-triphosphate (ATP) functions as a neurotransmitter or neuromodulator in the brain. To understand the role of ATP during brain development, we investigated the effects of ATP on morphology of cultured astrocytes obtained from the cerebral cortices of embryonic day 18 (E18) and postnatal day 2 (PN2) rats. In E18 astrocytes, ATP (10-1000 microM) alone did not affect astrocyte morphology, but significantly suppressed astrocyte stellation induced by the beta-adrenoceptor agonist isoproterenol or the membrane-permeable cyclic AMP analog dibutyryl cyclic AMP. The suppressive effect of ATP in embryonic astrocytes was selectively mimicked by P2U purinoceptor agonists. ATP had no effect on stellation induced by the protein kinase C (PKC) activator phorbol ester. It is probable that ATP, via P2U purinoceptors, suppresses cyclic AMP-dependent regulatory mechanism for stellation in embryonic astrocytes. On the other hand, PN2 astrocytes differentiated into stellate cells in response to ATP. The ATP-stimulated stellation in PN2 astrocytes was mimicked by adenosine, and blocked by P1 purinoceptor antagonists. It is probable that ATP is broken down into adenosine, which stimulates P1 purinoceptors, inducing stellation in postnatal astrocytes. These findings suggest that the effect of ATP on astrocyte stellation is switched from suppressive (P2U purinoceptor-mediated) to stimulatory (P1 purinoceptor-mediated) during late embryonic to neonatal stages. ATP may be a critical factor that determines timing of astrocyte differentiation during development.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan. kazuhoab@mol.f.u-tokyo.ac.jp
Saito
H
H
D000227:Adenine Nucleotides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000502:physiology / Q000648:ultrastructure*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000648:ultrastructure; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D000227:Adenine Nucleotides; D000318:Adrenergic beta-Agonists; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D007545:Isoproterenol; D013805:Theobromine