Carbon Monoxide: a Putative Neural Messenger

Abstract

Carbon monoxide, an activator of guanylyl cyclase, is formed by the action of the enzyme heme oxygenase. By in situ hybridization in brain slices, discrete neuronal localization of messenger RNA for the constitutive form of heme oxygenase throughout the brain has been demonstrated. This localization is essentially the same as that for soluble guanylyl cyclase messenger RNA. In primary cultures of olfactory neurons, zinc protoporphyrin-9, a potent selective inhibitor of heme oxygenase, depletes endogenous guanosine 3',5'-monophosphate (cGMP). Thus, carbon monoxide, like nitric oxide, may be a physiologic regulator of cGMP. These findings, together with the neuronal localizations of heme oxygenase, suggest that carbon monoxide may function as a neurotransmitter.

Presynaptic plasticity: The regulation of Ca2+-dependent transmitter release

“…Other free radicals may function in this way, like carbon monoxide (see Verma et al, 1993). Another potential new group is the polyamines which can be released from postsynaptic cells in a Ca 2+ dependent manner and can modulate presynaptic transmitter release (Bondy and Walker, 1986;Fage et al, 1992).…”

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

“…Since NOS is a hemoprotein, CO is able to bind to the existing NOS and inactivate the molecule. Conversely, NO could modulate HO-2 activity through free radical attack on ÀSH groups on HO-2 (Verma et al, 1993;Maines, 1997;Juckett et al, 1998). Ischiropoulos et al (1996) have found that CO exposure leads to the perivascular accumulation of nitrotyrosine, a marker of peroxynitrite (OONO À ) production.…”

“…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).…”

Prenatal carbon monoxide impairs migration of interneurons into the cerebral cortex

“…10a). CO acts as an agonist to soluble gunanylate cyclase similar to NO, and can also result in the formation of cGMP (Verma et al, 1993). Our early expectation was that CO exposure would result in an increase in cGMP.…”