NO donors stimulate noradrenaline release from rat hippocampus in a calmodulin-dependent manner in the presence ofL-cysteine

Publisher Website
Google Scholar
Abstract
Nitrogen oxides (NO) such as nitric oxide have been suggested to potentiate neurotransmitter release in a variety of neuronal cells. In this study, we showed that NO donors stimulate the release of noradrenaline (NA) from rat hippocampus both in vivo and in vitro. Co‐addition of NO donors (sodium nitroprusside [SNP] or S‐nitroso‐N‐acetylpenicillamine [SNAP]) and thiol compounds (dithiothreitol [DTT] or L‐cysteine) stimulated [3H]NA release from prelabeled hippocampal slices. Microdialysis in freely moving rats was used to ascertain the role of NO in control of NA release from the hippocampus in vivo. Co‐addition of SNAP and L‐cysteine stimulated endogenous NA release within 30 min. The concentration of NA peaked between 30–60 min to almost 3 times basal level. Another thiol compound, glutathione, had no effect on [3H]NA release in the presence of SNP or SNAP. In the presence of SNAP, the effect of L‐cysteine was much higher than that of the D‐isomer, although SNAP did not show stereospecificity. The effect of SNAP/L‐cysteine was rapid and the maximal increase in [3H]NA release was attained 0–1 min after application, which was similar in time course to the effect of KCl. Unlike the release by KCl, SNAP/L‐cysteine‐stimulated NA release was independent of extracellular CaCl2. However, pretreatment with the calmodulin antagonists W‐7 or trifluoperazine significantly reduced the SNAP/L‐cysteine‐stimulated [3H]NA release. Formation of nitric oxide and activation of guanylate cyclase by nitric oxide were not responsible for SNAP/L‐cysteine‐stimulated NA release. These findings suggest that NO donors stimulate NA release from the hippocampus in the presence of thiol compounds such as L‐cysteine in vivo and in vitro in a calmodulin‐dependent, Ca2+‐ and cyclic GMP‐independent manner. The physiological roles of thiol compounds such as L‐cysteine or glutathione as intermediates of NO are discussed.