Electrophysiological techniques and Xenopus oocytes were used to study the expression of neurotransmitter receptors encoded by mRNAs isolated from three human glioma cell lines. Oocytes injected with mRNAs from two glioblastoma cell lines did not show electrical responses to the various neurotransmitters tested. In contrast, oocytes in ected with mRNA from an astrocytoma cell line (R-1l1) acquired acetylcholine and glutamate receptors as well as a small number of N-methyl-D-aspartate (NMDA) receptors. Acetylcholine elicited oscillatory Cl-currents that were abolished by muscarinic antagonists. The muscarnic receptors are coupled to the inositol phosphate-Ca2+ receptor-channel coupling system. Glutamate and its analogs kainate, quisqualate, and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid induced smooth currents. The non-NMDA responses were potently blocked by 6,7-dinitroquinoxaline-2,3-dione. Our results show that human astrocytoma cells contain mRNAs coding for functional acetylcholine and glutamate receptors that have properties similar to those of neurons. In contrast, human glioblastoma cells lacked those mRNAs. These differences might be useful for the development of new diagnostic and therapeutic procedures.Tumor cells of the brain, like other neoplastic cells, are known to release cytokines, growth-controlling factors, and other substances involved in cell regulation (1-3). It is, therefore, important to determine the pattern of receptors expressed in the membrane of tumor cells, as this may help us understand the way tumors develop and the way they modulate the immune system of the host. Such knowledge would also be very useful for the development of new diagnostic and therapeutic procedures.Electrophysiological studies have already shown that glial cells possess receptors to glutamate and other neurotransmitters (4-8). However, most of that work was done on murine cells in culture, and it is known that the procedures used to isolate the cells, as well as the culture process itself, can alter the types and properties of the receptors expressed (9, 10). Moreover, the receptors in murine cells might differ importantly from those present in human cells. It is thus necessary to study the human cells directly and, although human cells in vitro seem to undergo fewer genetic transformations than murine cells, it would be preferable not to use cultured cells. Indeed, human brain tumors have been found to express some neurotransmitter receptors (12-15). However, these studies used labeled ligand binding and autoradiography to characterize the receptors, and little information was gained about their functional properties.To avoid some of the problems mentioned above we decided to use a different approach to determine the presence of mRNAs coding for neurotransmitter receptors in human tumors borne in nude mice. To that effect, mRNA, isolated from the tumors, was injected into Xenopus oocytes, which have been shown to be a highly efficient system for expressing various functional foreign receptors ...
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