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 mu M) 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 P-2U purinoceptor agonists. ATP had no effect on stellation induced by the protein kinase C (PKC) activator phorbol ester. It is probable that ATP, via P-2U 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 P-1 purinoceptor antagonists. It is probable that ATP is broken down into adenosine, which stimulates P-1 purinoceptors, inducing stellation in postnatal astrocytes. These findings suggest that the effect of ATP on astrocyte stellation is switched from suppressive (P-2U putinoceptar-mediated) to stimulatory (P-1 purinoceptor-mediated) during late embryonic to neonatal stages. ATP may be a critical factor that determines timing of astrocyte differentiation during development. (C) 1999 Elsevier Science B.V. All rights reserved.