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Glutamate regulates adenylate cyclase and guanylate cyclase activities in an isolated membrane preparation from insect muscle

Abstract

It is generally believed that glutamate serves as a neurotransmitter at many vertebrate and invertebrate synapses. There is, however, little information concerning the possible involvement of cyclic nucleotides as intracellular second messengers for any of the postsynaptic actions of glutamate. Direct activation of adenylate cyclase has been reported for several neurotransmitters and neuromodulators1, but no such effect has been reported for glutamate. Moreover, although several neurotransmitters including glutamate have been shown to increase cyclic GMP levels in intact preparations of nerve and muscle tissue2,3 apparently by promoting Ca2+ entry into the cells, no neurotransmitter has been shown to activate guanylate cyclase in a cell-free preparation. L-Glutamate is the prime candidate for the neurotransmitter at the excitatory neuromuscular synapses in insects4. Moreover, recent studies have shown that glutamate application raises both cyclic AMP5 and cyclic GMP levels (P.M.C., unpublished observations) in insect muscle. To determine the mechanism underlying these increases, we have studied the effect of glutamate in a membrane fraction prepared from this muscle, and report here that the neurotransmitter activates both adenylate cyclase and guanylate cyclase in the membrane preparation, and that the activation by glutamate of guanylate cyclase is calcium independent.

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Robinson, N., Cox, P. & Greengard, P. Glutamate regulates adenylate cyclase and guanylate cyclase activities in an isolated membrane preparation from insect muscle. Nature 296, 354–356 (1982). https://doi.org/10.1038/296354b0

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