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Modulation of Neuronal Signal Transduction Systems by Extracellular ATP
Author(s) -
Ehrlich Y. H.,
Snider R. M.,
Kornecki E.,
Garfield M. G.,
Lenox R. H.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb13263.x
Subject(s) - extracellular , intracellular , second messenger system , inositol , biophysics , stimulation , biochemistry , gtp' , aequorin , biology , adenylate kinase , chemistry , microbiology and biotechnology , receptor , endocrinology , enzyme
The secretion of ATP by stimulated nerves is well documented. Following repetitive stimulation, extracellular ATP at the synapse can accumulate to levels estimated to be well over 100 μ M. The present study examined the effects of extracellular ATP in the concentration range of 0.1–1.0 m M on second‐messenger‐generating systems in cultured neural cells of the clones NG108‐15 and NIE‐115. Cells in a medium mimicking the physiological extracellular environment were used to measure 45 Ca 2+ uptake, changes in free intracellular Ca 2+ levels by the probes aequorin and Quin‐2, de novo generation of cyclic GMP and cyclic AMP from intracellular GTP and ATP pools prelabeled with [ 3 H]guanosine and [ 3 H]adenine, respectively, and phosphoinositide metabolism in cells preloaded with [ 3 H]inositol and assayed in the presence of LiCI. Extracelluar ATP induced a concentration‐dependent increase of 45 Ca 2+ uptake by intact cells, which was additive with the uptake induced by K + depolarization. The increased uptake involved elevation of intracellular free Ca 2+ ions, evidenced by measuring aequorin and Quin‐2 signals. At the same concentration range (0.1–1.0 m M ), extracellular ATP induced an increase in [ 3 H]cyclic GMP formation, and a decrease in prostaglandin E 1 ‐stimulated [ 3 H]cyclic AMP generation. In addition, extracellular ATP (1 m M ) caused a large (15‐fold) increase in [ 3 H]inositol phosphates accumulation, and this effect was blocked by including La 3+ ions in the assay medium. In parallel experiments, we found in NG 108–15 cells surface protein phosphorylation activity that had an apparent K m for extracellular ATP at the same concentration required to produce half‐maximal effects on Ca 2+ uptake. Extracellular ATP at concentrations that can be produced in the synaptic cleft by repetitive stimulation but not during routine transmission can thus initiate a unique chain of events, which may play a role in the induction of long‐term adaptive changes in neuronal function.