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Abstract: The aim of the present study was to investigate, whether dopamine D1 and/or D2 receptors are able to interfere with the ATP-induced increase of the intracellular Ca2+ concentration ([Ca2+]i) in cultured striatal neurons identified by their morphological characteristics and their [Ca2+]i transients in response to a high-K+ superfusion medium. ATP appeared to release Ca2+ mostly from an intracellular pool, since its effect was markedly depressed in the presence of cyclopiazonic acid, which is known to deplete such storage sites [Rubini, P., Pinkwart, C., Franke, H., Gerevich, Z., Nörenberg, W., Illes, P., 2006. Regulation of intracellular Ca2+ by P2Y1 receptors may depend on the developmental stage of cultured rat striatal neurons. J. Cell. Physiol. 209, 81–93]. The mixed D1/D2 receptor agonist dopamine increased the ATP-induced [Ca2+]i transients in a subpopulation of neurons. At the same time, dopamine did not alter the responses to K+ in these cells. The selective D1 (SKF 83566) and D2 (sulpiride) receptor antagonists failed to modify the effect of ATP, but unmasked in the previously unresponsive neurons an inhibitory and facilitatory effect of dopamine, respectively. A combination of the two antagonists resulted in a failure of dopamine to modulate the [Ca2+]i responses in any cell investigated. In conclusion, D1 and D2 receptors may modulate in an opposite manner the signalling pathways of P2Y1 receptors in striatal neurons and thereby alter their development/growth or their cellular excitability and/or the release of GABA from their terminals. [Copyright &y& Elsevier]

Abstract: A combined real-time PCR/immunohistochemistry study was carried out to investigate whether P2X7 receptors, known to induce apoptosis and necrosis, may be causally related to the process of retinal degeneration in BALBCrds mice. In the retinae of BALBCrds mice, P2X7 receptor-mRNA was the highest at an age of 20–40 days, and declined afterwards. At the same time, the P2X7 receptor-message was constantly low in the retina of control BALBC mice until postnatal day 100. The receptor-mRNA in total brain tissue of both strains of mice was comparable with that of BALBCrds retinae. Double immunofluorescence in combination with laser scanning microscopy was used to study the distribution of P2X7 receptor-immunoreactivity (IR) on neurons and different glial cell types of the retina. An exclusively neuronal localization of P2X7-IR in the ganglion cell layer was found by using either anti-neuronal nuclei or microtubule associated protein-2 as neuronal markers. There was a slight age-dependent decrease in the abundance of neuronal P2X7-IR both in BALBCrds or BALBC mice. P2X7-IR failed to co-localize with any of the non-neuronal markers used to stain microglial or Müller glial cells. No P2X7 receptor-IR was found in the retinal ganglion cell layer of P2X7 −/− animals, when compared with the control littermates. Hence, we suggest that, in BALBCrds mice, an early up-regulation of neuronal P2X7 receptors may cause injury of retinal neurons and thereby functionally contribute to the retinal damage. [Copyright &y& Elsevier]

In the 1st part of this study, monosynaptic excitatory postsynaptic potentials (EPSPs) in layer V of the rat prefrontal cortex (PFC) were evoked by electrical stimulation of layer I. Recordings with intracellular sharp, microelectrodes showed a concentration-dependent inhibition of the EPSP by adenosine 5′-O-(2-thiodiphosphate) (ADP-β-S). Pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), when given alone depressed the EPSP and in addition antagonized the effect of ADP-β-S. Exclusion of the N-methyl-d-aspartate (NMDA) component of the EPSP by d(·)-amino-5-phosphonopentanoic acid (AP-5) abolished the ADP-β-S-induced depression. The pressure-application of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) caused reproducible depolarizations. ADP-β-S inhibited the effect of NMDA, but did not alter that of AMPA. PPADS was also under these conditions antagonistic with ADP-β-S. In the 2nd part of the study, NMDA-induced currents were measured by whole-cell patch-clamp pipettes. ADP-β-S caused a concentration-dependent inhibition of the responses to NMDA. PPADS alone did not alter the NMDA-currents but again antagonized the action of ADP-β-S; 2′-deoxy-N6-methyladenosine-3′,5′-diphosphate (MRS 2179) also abolished the NMDA effect. The ADP-β-S-induced inhibition persisted in the presence of tetrodotoxin (TTX) or guanosine 5′-O-(3-thiodiphosphate) (GDP-β-S) applied to the external medium and the pipette solution, respectively. The 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) moderately decreased the ADP-β-S effect. The inhibitory function of ADP-β-S on EPSPs and the interaction with PPADS was observed also in layer V pyramidal neurons of the parietal somatosensory cortex. In conclusion, metabotropic P2Y1 receptors appear to exert a new modulatory influence on fast excitatory amino acid transmission in the cerebral cortex. [Copyright &y& Elsevier]