Tissue distribution and physiorogical function of ATP receptors

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P2 purinoceptor mRNA expression in the central nervous system was examined by the reverse transcription-coupled polymalase chain reaction (RT-PCR) with 11 different P2 receptor subtype-specific primers. Under an optimal condition, P2X_4 and P2X_6 receptors were found to be dominant P2X ionotropic receptors in rat brain. P2X_7 receptor mRNA was also ubiquitously expressed to a lesser extent. P2X_2 and P2X_5 receptor mRNAs exhibited more discrete distribution, localized in midbrain, brain stem and spinal cord. P2 X_3 was only detected in the brain stem and spinal cord. P2X_1 was little expressed in the rat brain. In contrast, G protein-coupled P2Y receptor subtypes were widely distributed in the brain and relative amount was P2Y_1≧P2Y_2≧P2Y_4>P2Y_6. During the postnatal development, P2X_2 receptor mRNA was highly expressed in many brain regions and progressively decreased during the development. In contrast, P2Y_2 and P2Y_6 receptors were increased. These results demonstrate that several P2 receptors were expressed in the rat brain in a region specific and development-dependent manner.On the other hand, a unique ATP-induced response that did not fit with any cloned P2 receptors was found in cell lines derived from the central nervous system. This response was identified as an event occurring in a membrane surface microdomain where extracellular ATP was rapidly and quantitatively converted into adenosine by ectonucleotidases, resulting in activation of P1 adenosine receptors. This ATP-induced response was somewhat more potent than adenosine-induced one. It is therefore suggested that ecto-nucleotidases and P1 receptors are closely localized in the membrane surface, and functionally couple to respond to ATP.