Journal of neurochemistry
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Journal of neurochemistry · Nov 1999
Nitric oxide-independent down-regulation of soluble guanylyl cyclase by bacterial endotoxin in astroglial cells.
Induction of nitric oxide (NO) synthase (NOS) type 2 (NOS-2) in glial cells after exposure to bacterial endotoxin [lipopolysaccharide (LPS)] or inflammatory cytokines has been repeatedly demonstrated both in vitro and in vivo. However, little is known about effects of these agents on NO-dependent cyclic GMP (cGMP) formation. In this work, we show that treatment of rat cerebellar astrocyte-enriched primary cultures with LPS decreases NO donor-stimulated cGMP formation with a similar initial time course (up to 9-12 h) and concentration dependency (0.1-1 ng/ml) as for induction of NOS-2. ⋯ LPS impairment of cGMP formation also occurs in cortical astrocytes but not in cerebellar granule neurons. The decreased responsiveness of sGC to NO stimulation following LPS challenge may prevent inappropriate astroglial cGMP signaling caused by excess production of NO by adjacent activated glial cells. Key Words: Astroglia-Neurons-Nitric oxide-Soluble guanylyl cyclase-Lipopolysaccharide.