ATP has been shown to be an important extracellular signaling molecule. There are two subgroups of receptors for ATP (and other purines and pyrimidines): the ionotropic P2X and the G-protein-coupled P2Y receptors. Different subtypes of these receptors have been identified by molecular biology, but little is known about their functional properties in the nervous system. Here we present data for the existence of P2 receptors in Müller (glial) cells of the human retina. The cells were studied by immunocytochemistry, electrophysiology, Ca(2+)-microfluorimetry, and molecular biology. They displayed both P2Y and P2X receptors. Freshly enzymatically isolated cells were used throughout the study. Although the [Ca(2+)](i) response to ATP was dominated by release from intracellular stores, there is multiple evidence that the ATP-induced membrane currents were caused by an activation of P2X(7) receptors. Immunocytochemistry and single-cell RT-PCR revealed the expression of P2X(7) receptors by Müller cells. In patch-clamp studies, we found that (1) benzoyl-benzoyl ATP (BzATP) was the most effective agonist to evoke large inward currents and (2) the currents were abolished by P2X antagonists; however, (3) long-lasting application of BzATP did not cause an opening of large pores in addition to the cationic channels. By microfluorimetry it was shown that the P2X receptors mediated a Ca(2+) influx that contributed a small component to the total [Ca(2+)](i) response. Activation of P2X receptors may modulate the uptake of neurotransmitters from the extracellular space by Müller cells in the retina.

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Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-γ), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-α, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-γ and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-α, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-α, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.

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Excitatory ATP responses in rat cultured thoracolumbar sympathetic neurones are mediated by somatic P2X 2 receptors. The present study investigated a possible role of axonal P2X 2 as well as P2X 7 receptors on the same preparation. Confocal laser scanning microscopy demonstrated P2X 2 and P2X 7 immunoreactivity along the axons as well as P2X 7 immunoreactivity surrounding the cell nuclei. P2X 7 mRNA expression was detected in individual neurones using a single-cell RT-PCR approach. Adenosine triphosphate (ATP) caused a significant increase in axonal Ca 2+ concentration which was dependent on external Ca 2+ but insensitive to depletion of the cellular Ca 2+ pools by cyclopiazonic acid.Pyridoxal-phosphate-6-azophenyl-2¢,4¢-disulfonate (PPADS; 30 lM) virtually abolished the ATP response, whereas brilliant blue G (0.1 lM), a selective P2X 7 receptor antagonist, had no effect. Dibenzoyl-ATP (BzATP; 100 lM) induced a much smaller increase in axonal [Ca 2+ ] concentration than ATP at equimolar concentrations. The response to BzATP was distinctly reduced by PPADS but not by brilliant blue G. The overall pharmacological profile of the axonal P2X receptors resembled closely that of the somatic P2X 2 receptors. In conclusion, the present data suggest the occurrence of axonal excitatory P2X 2 receptors in thoracolumbar sympathetic neurones. However, the functional significance of axonal and (peri)-nuclear P2X 7 receptors has still to be proven.