Expression of P2X purinoceptors during rat brain development and their inhibitory role on motor axon outgrowth in neural tube explant cultures

Extracellular ATP is well known as a neurotransmitter and neuromodulator in the CNS of adults. However, little is known about the involvement of ATP during the development of mammalian brain. In the present study, we have examined the expression pattern of P2X receptor subtype mRNA and protein during perinatal rat brain development (from embryonic day (E) 10 to postnatal day (P) 16 brain). While P2X(3) receptors appeared early at E11, they declined in the stages that follow. P2X(2) and P2X(7) receptors were expressed from E14 onwards, while P2X(4), P2X(5) and P2X(6) receptors were expressed from P1 onwards. P2X(1) receptor expression was not observed in any of the developmental ages examined. We investigated the effect of 100 mu M ATP and alpha,beta-methylene ATP (alpha,beta-meATP; selective agonist for P2X(1), P2X(2/3) and P2X(3) receptors) on motor axon outgrowth in collagen-embedded neural tube explant cultures. Both ATP- and alpha,beta-meATP-treated neural tubes showed a significant reduction in neurite outgrowth compared with the control explants. This inhibitory effect could not be reproduced by uridine triphosphate. In conclusion, all P2X receptor subtypes, except for P2X(1), were strongly represented in the developing rat brain. ATP was shown to inhibit motor axon outgrowth during early embryonic neurogenesis, most likely via the P2X(3) receptor. It is speculated that P2X(7) receptors may be involved in programmed cell death during embryogenesis and that P2X(4), P2X(5) and P2X(6) receptors might be involved in postnatal neurogenesis. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.