| dc.description.abstract | Iron, an essential element for living organisms, participates in a wide range of metabolic processes. It appears predominantly firmly bound to proteins, but can also be loosely bound to low-affinity ligands, referred as labile iron pool (LIP). The composition and amount of LIP can vary considerably under different physiological conditions, playing a beneficial role in iron economy and homeostasis or contributing to the generation of reactive oxygen species. It is still not known if bioactivity of low-affinity ligands can be modulated by iron binding. Catecholamine neurotransmitters including norepinephrine (NE) can chelate iron. In the close vicinity of synaptic cleft, astrocytes are direct target of norepinephrine. Here we show on cultured rat cortical astrocytes that iron bound to NE completely blocks neurotransmitter activity of NE. However, how astrocyte activity changes when norepinephrine binds iron remains unknown. We show, using spectrophotometry that NE and Fe3+ form complex in the 1:1 stoichiometry, at pH 7.4. Iron effect on astrocyte response to NE was examined by the whole-cell patch-clamp technique. NE alone evokes changes in the membrane currents of astrocytes, but such effects were not observed for the NE- Fe3+ complex. Our results demonstrating that iron in the complex with norepinephrine inhibits alpha-adrenergic receptors and modulates astrocyte activity, imply a novel neuromodulatory role for LIP. | sr |
