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Title: Functional aspects of P2 receptor signalling in the rat central nervous system
Author: Bennett, Gillian C.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2000
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Adenosine 5'-triphosphate (ATP), exerts an effect on receptors termed 'P2 receptors', which can be divided into ionotropic 'P2X' receptors and metabotropic 'P2Y' receptors. ATP is released from peripheral and central nerve terminals and is well established as a fast excitatory transmitter, acting through P2X receptors. However, relatively little evidence has emerged to demonstrate the presence of P2Y receptors in the central nervous system (CNS), although pre- and post-synaptic expression have been shown in the periphery. The aim of this study was therefore to study some consequences of P2Y receptor activation in preparations of rat brain cortex, and to attempt identification and localisation of receptor subtypes. The relatively stable analogue of ATP, ATPS, enhanced total inositol phosphate accumulation in lithium blocked rat cortical slices, indicating that phospholipase C-linked P2 receptors were present and functional. Cerebrocortical primary cultures were made, and nucleotide-mediated Ca2+ transients studied, which indicated the presence of P2Y1 receptors on glia and P2X receptors on neurones. KC1-evoked glutamate release from cortical slices was measured and an inhibitory, modulatory effect of ATP, ADP, ATPS and adenosine established. The A1 receptor antagonist, DPCPX, blocked the inhibitory effect of both ATP and adenosine whereas the P2 receptor antagonist, Cibacron Blue 3GA, inhibited evoked glutamate release when tested alone, augmented the inhibition shown by ATP but had no effect on adenosine inhibitions. Hypotheses are proposed to explain these effects. Finally, RT-PCR showed the presence of P2Y4 and P2Y6 mRNA in adult and embryonic rat cortical tissue, cerebrocortical cells and glial cell cultures. P2Y1 mRNA was found in all preparations with the exception of adult cortical tissue, and P2Y2 mRNA was found in all but embryonic cortical tissue. It is concluded that P2Y receptors are present and functional in a variety of rat cortical preparations and may exert a widespread influence on brain function.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available