HO/CO and NO Regulate Oxytocin - Anxiety and Autism Implications?

Considering the relationship of oxytocin to behaviors such as fear, aggression and attachment, this study may have significant implications for PTSD as well as social problems such as violence and neglect. Also, it presents a question of whether a decline in the antioxidant system may also positively or negatively have an influence because it regulates HO-1.

Blockade of HO inhibited both basal and osmotically stimulated OT release, and induced a marked increase in NOS activity. These results indicate the involvement of CO in the regulation of NOS activity. The present data demonstrate that hypothalamic OT release induced by osmotic stimuli is modulated, at least in part, by interactions between NO and CO.

CiteULike: Carbon monoxide and nitric oxide modulate hyperosmolality-induced oxytocin secretion by the hypothalamus in vitro.: "Gomes, D. A. A., Giusti-Paiva, A., Ventura, R. R. R., Elias, L. L. K. L., Cunha, F. Q. Q., and Antunes-Rodrigues, J. (2010). Carbon monoxide and nitric oxide modulate hyperosmolality-induced oxytocin secretion by the hypothalamus in vitro. Bioscience reports, 30(5):351-357."

HO-2 and Nitric Oxide Synthase Immunoreactivity of Bovine Olfactory Receptor Neurons and a Comparison with the Distribution of NADPH-diaphorase Staining

The coincident localization of the moderate NADPH-d activity and heme oxygenase-2 immunoreactivity in receptor cell perikarya suggest a functional association between NADPH-cytochrome P450 reductase and heme oxygenase-2. In contrast, dendritic localization of NADPH-d activity is topically and possibly functionally related to the presence of the inducible isoform of NOS. The results suggest that both CO and NO may be generated in bovine receptor neurons and thus involved in odorant stimulation. Based on immunocytochemical localization of synthesizing enzymes, NO might be regarded as a direct regulator of transduction related processes while CO might act as a modulator of the initial signal.

Heme Oxygenase-2 and Nitric Oxide Synthase Immunoreactivity of Bovine Olfactory Receptor Neurons and a Comparison with the Distribution of NADPH-diaphorase Staining: "Wenisch, S., Andressen, C., Derouiche, A., Arnhold, S., Addicks, K., and Leiser, R. (2000). Heme oxygenase-2 and nitric oxide synthase immunoreactivity of bovine olfactory receptor neurons and a comparison with the distribution of nadph-diaphorase staining. The Histochemical Journal, 32(6):381-388."

H2s is a gasoneurotransmitter and is regulated by HO-1 through Nrf2. The other two gasoneurotransmitters are NO and CO and we suggest there may a similar mode of action between protection and poisoning from all three – regulated by HO-1. Bauer writes, “The protective effects of exogenous CO may strongly depend on the pathological condition, the mode, time point and duration of application, the administered concentration, and on the target tissue and cell. Differences in bioavailability of endogenous CO-production and exogenous CO supplementation might also provide an explanation for the lack of protective effects observed in some experimental and in clinical studies.” H2S may be comparable and as this author points out, more research is needed.


Bauer, I. and Pannen, B. (2009). Bench-to-bedside review: Carbon monoxide – from mitochondrial poisoning to therapeutic use. Critical Care, 13(4):220+.http://www.citeulike.org/user/HEIRS/article/5439821