Abstract
The effect of nitric oxide on synaptic vesicle proton gradient and membrane potential of rat brain nerve terminals was studied. It has been shown that nitric oxide in the form of S-nitrosothiols at nanomolar concentrations had no effect on the studied parameters, but caused a rapid dissipation of synaptic vesicle proton gradient and depolarization of mitochondrial membrane in the presence of a SH-reducing compound such as dithiothreitol. Both processes were reversible and the rate of H(+)-gradient restoration depended on the redox potential of nerve terminals, namely the molar ratio of reductant/oxidant. This facts, as well as insensitivity of the studied processes to the inhibitor of NO-sensitive guanylate cyclase such as ODQ, allow suggesting that post-translational modification of thiol residues of the mitochondrial and synaptic vesicle proteins underlies the effect of nitric oxide on the key functional parameters ofpresynaptic nerve terminals.
Highlights
Nitric oxide (NO) is a unique signaling mole cule that is involved in the development of many physiological and pathophysiological processes in the body
Nitric oxide synthesized in the postsynaptic neuron following the activation of, for example, the NMDA-type glutamate receptors can act as a retrograde messenger diffusing into the presynaptic terminals and modulating the release of almost all known neurotransmitters [3]
Nitric oxide can act after being released from the NO-synthesizing specific neurons or NO donors, some of which are used as drugs
Summary
Nitric oxide (NO) is a unique signaling mole cule that is involved in the development of many physiological and pathophysiological processes in the body. According to one of them, NO modulates neurotransmission processes activating soluble guanylate cyclase, which triggers an intracellular signaling cascade via c-GMP, a secondary messenger [4, 5]. This mecha nism is believed to be physiological and activated at very low NO concentrations (in the range of pico- to nanomol) that are produced during operation of the constitutive isoforms of NO-synthase [6]. S-nitrosylation of thiol groups of neuronal pro teins, alteration in activity of which affects neuro transmission, is another mechanism of biological action of nitric oxide at the presynapse. SNAP belongs to the class of S‐nitrosothiols, which are natural metabolites of nitricoxide and in the form of which NO is mostly stored and transported in cells [13]
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