Carbon Monoxide: An Endogenous Modulator of the Nitric Oxide–Cyclic GMP Signaling System

Ingi, Tatsuya; Cheng, Julia N.; Ronnett, Gabriele V.

doi:10.1016/s0896-6273(00)80103-8

Cited by 234 publications

(172 citation statements)

References 48 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…In rat brain slices, electrical field stimulation leads to Ca 2ϩ waves spreading from the astrocytic soma to the end feet (11). In the present study, we observed that glutamate causes Ca 2ϩ transients at 10 CO production has been measured in neurons (16), vascular smooth muscle cells (21,29), endothelial cells (21), and astrocytes (this study). In the cerebral vasculature, glutamate stimulates CO production in astrocytes (26) and endothelial cells (21).…”

Section: Discussionsupporting

confidence: 66%

Glutamate-induced calcium signals stimulate CO production in piglet astrocytes

Tcheranova

Basuroy

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Glutamate-stimulated, astrocyte-derived carbon monoxide (CO) causes cerebral arteriole dilation by activating smooth muscle cell large-conductance Ca 2ϩ -activated K ϩ channels. Here, we examined the hypothesis that glutamate activates heme oxygenase (HO)-2 and CO production via the intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i)/ Ca 2ϩ -calmodulin signaling pathway in newborn pig astrocytes. The major findings are: 1) glutamate stimulated Ca 2ϩ transients and increased steady-state [Ca 2ϩ ]i in cerebral cortical astrocytes in primary culture, 2) in astrocytes permeabilized with ionomycin, elevation of [Ca 2ϩ ]i concentration-dependently increased CO production, 3) glutamate did not affect CO production at any [Ca 2ϩ ]i when the [Ca 2ϩ ]i was held constant, 4) thapsigargin, a sarco/endoplasmic reticulum Ca 2ϩ -ATPase blocker, decreased basal CO production and blocked glutamate-induced increases in CO, and 5) calmidazolium, a calmodulin inhibitor, blocked CO production induced by glutamate and by [Ca 2ϩ ]i elevation. Taken together, our data are consistent with the hypothesis that glutamate elevates [Ca 2ϩ ]i in astrocytes, leading to Ca 2ϩ -and calmodulin-dependent HO-2 activation, and CO production. cerebral circulation; heme oxygenase; calmodulin; gasotransmitter; neurovascular coupling IN THE NEUROVASCULAR UNIT, astrocytes act as intermediaries between neurons and arterioles to regulate vascular tone in response to neuronal activity. Release of glutamate from presynaptic neurons increases blood flow to match metabolic demands; such coupling is called functional hyperemia. Functional hyperemia has been investigated extensively, and many astrocyte-derived vasoactive mediators, including ADP (40, 41), ATP (34, 36), epoxyeicosatrienoic acids (1-3), K ϩ (11, 13, 33), and prostacyclin (42), appear to be involved, depending on experimental models. We have shown that carbon monoxide (CO) is another critical regulator of cerebrovascular tone in newborn piglets (19,24,26,31,39).CO dilates newborn pig pial arterioles (22,25). CO causes vasodilation by stimulating Ca 2ϩ sparks and large-conductance Ca 2ϩ -activated K ϩ (BK Ca ) channels and by increasing effective coupling between Ca 2ϩ sparks and BK Ca channels in arterial smooth muscle cells (17,18,25,38). Physiologically, CO is produced by heme oxygenase (HO)-catabolized breakdown of heme to CO, iron, and biliverdin (27). Of three HO isoforms, only HO-2 is expressed under basal conditions in newborn piglet brain (31, 32). In piglets, endogenous HO-2 can produce sufficient CO to induce cerebral arteriole dilation (23).Our previous studies in piglets demonstrated that glutamate stimulates astrocytic CO production in primary-cultured astrocytes and in vivo (24,26,31). We also demonstrated that astrocytes release CO and astrocyte-derived CO causes glutamate-induced pial arteriolar dilation in vivo (24), supporting a regulatory role for astrocytic CO in neurovascular coupling in the newborn brain. Indeed, in brain slices from newborn piglets, we demonstrated that glut...

show abstract

Section: Discussionsupporting

confidence: 66%

Glutamate-induced calcium signals stimulate CO production in piglet astrocytes

Tcheranova

Basuroy

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…(i) In vitro, micromolar concentrations of CO have been shown to impair DNA binding and BMAL-heterodimer formation of heme-bound NPAS2 but not apo-NPAS2 (ref. 6), and in the brain, these concentrations of CO are generated by heme oxygenases 32 (detailed discussion of CO concentration in Supplementary Note 1). (ii) Mutation of heme-coordinating residues within NPAS2 also impairs heterodimer formation with BMAL1, thus decreasing both specific DNA binding to canonical E boxes and NPAS2-BMAL1 transactivation activity, probably via conformational changes within the PAS-A domain of NPAS2 (ref.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal regulation of carbon monoxide metabolism and the circadian clock

Klemz

Reischl

Wallach

et al. 2016

Nat Struct Mol Biol

View full text Add to dashboard Cite

“…HO-3 is a recently identified isoform and appeares to regulate heme-dependent genes (Magnusson et al, 2000). CO, like nitric oxide (NO), binds to the heme moeity of soluble guanylate cyclase (sGC) (Brune et al, 1990;Verma et al, 1993;Ingi et al, 1996a;Snyder et al, 1998) and in cultured olfactory neurons HO inhibitors reduce cGMP levels (Ingi et al, 1996b). Cytochrome c oxidase, the terminal enzyme in the mitochondrial electron transport chain, is another potential target for the actions of CO in the cell (Piantadosi, 1996).…”

Section: Introductionmentioning

confidence: 99%

Effect of Carbon Monoxide on Dopamine and Glutamate Uptake and cGMP Levels in Rat Brain

Taşkıran

Kutay

Pöğün

2002

Neuropsychopharmacol

View full text Add to dashboard Cite

After the recognition of nitric oxide (NO) as a messenger molecule in the nervous system, carbon monoxide (CO) has received attention with similar properties. The present study aims to elucidate the effects of CO on synaptosomal dopamine ( 3 H-DA) and glutamate ( 3 H-Glu) uptake and on cGMP levels; possible interaction between NO and CO systems was also evaluated. Our results provide evidence for the inhibition of DA and Glu uptake by CO in a time-, dose-, and temperature-dependent manner in rat striatum and hippocampus, respectively; the inhibition observed was sexually dimorphic with more pronounced effects in females. Basal cGMP levels were higher in female rats than males in the striatum and exogenous CO increased striatal cGMP levels only in males; no effect of CO was observed in the hippocampus. In vivo nitric oxide synthase (NOS) inhibition increased DA and Glu uptake; however, CO was still effective in inhibiting uptake following NOS inhibiton. Taken together, these findings suggest a role for CO in trans-synaptic regulation through modulation of DA and Glu transporters and of cGMP levels; the effect on cGMP levels is independent of NOS activity and appears to be sexually dimorphic and region specific.

show abstract

Carbon Monoxide: An Endogenous Modulator of the Nitric Oxide–Cyclic GMP Signaling System

Cited by 234 publications

References 48 publications

Glutamate-induced calcium signals stimulate CO production in piglet astrocytes

Glutamate-induced calcium signals stimulate CO production in piglet astrocytes

Reciprocal regulation of carbon monoxide metabolism and the circadian clock

Effect of Carbon Monoxide on Dopamine and Glutamate Uptake and cGMP Levels in Rat Brain

Contact Info

Product

Resources

About