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Regulation of Neuronal Nitric Oxide and Cyclic GMP Formation by Ca 2+
Author(s) -
Mayer Bernd,
Klatt Peter,
Böhme Eycke,
Schmidt Kurt
Publication year - 1992
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.1471-4159.1992.tb10090.x
Subject(s) - calmodulin , soluble guanylyl cyclase , second messenger system , nitric oxide , chemistry , cytosol , phosphodiesterase , intracellular , cyclase , biochemistry , nitric oxide synthase , cyclic gmp , biophysics , receptor , enzyme , biology , organic chemistry
Nitric oxide (NO) acts as a messenger molecule in the CNS by activating soluble guanylyl cyclase. Rat brain synaptosomal NO synthase was stimulated by Ca 2+ in a concentration‐dependent manner with half‐maximal effects observed at 0.3 μ M and 0.2 μ M when its activity was assayed as formation of NO and L‐citrulline, respectively. Cyclic GMP formation was apparently inhibited, however, at Ca 2+ concentrations required for the activation of NO synthase, indicating a down‐regulation of the signal in NO‐producing cells. Purified synaptosomal guanylyl cyclase was not inhibited directly by Ca 2+ , and the effect was not mediated by a protein binding to guanylyl cyclase at low or high Ca 2+ concentrations. In cytosolic fractions, the breakdown of cyclic GMP, but not that of cyclic AMP, was highly stimulated by Ca 2+ , and 3‐isobutyl‐1‐methylxanthine did not block this reaction effectively. The effects of Ca 2+ on cyclic GMP hydrolysis and on apparent guanylyl cyclase activities were abolished almost completely in the presence of the calmodulin antagonist calmidazolium, whose effect was attenuated by added calmodulin. Thus, a Ca 2+ /calmodulin‐dependent cyclic GMP phosphodiesterase is highly active in synaptic areas of the brain and may prevent elevations of intracellular cyclic GMP levels in activated, NO‐producing neurons.