Table 1.

Contrasting properties of neuronal NO synthase and HO2

	nNOS	HO2
Biosynthesis	Catalyzes a mixed oxidation of arginine to form the diatomic gas radical, NO.	Catalyzes a mixed oxidation of heme to form the inert diatomic gas, CO.
Gene isoforms	iNOS, inducible nNOS, eNOS, constitutive	HO1, inducible HO2, constitutive
Subcellular localization	Dendrites, axons, endoplasmic reticulum, and cytosol	Exclusively on the endoplasmic reticulum
Activation	Calcium/calmodulin	Protein kinase C
Target of gaseous messenger	Soluble guanyl cyclase	Soluble guanyl cyclase
	Can directly alter protein function by S-nitrosylation.	Other targets?
Role in blood vessels	Originally discovered as endothelial-derived relaxation factor	Like eNOS and nNOS, HO2 is present in both the endothelium and the surrounding adventitial neurons.
Role in gastrointestinal tract	Nonadrenergic, noncholinergic neurotransmitter, most prominently in the pylorus	Nonadrenergic, noncholinergic neurotransmitter, most prominently in the internal anal sphincter
Role in urogenital tract	nNOS+ neurons innervate the corpus cavernosum. NOS inhibitors prevent penile erections.	HO2+ neurons innervate the bulbospongiosus muscles. Ejaculation is reduced in HO2−/− mice.
Behavior	nNOS−/− mice are aggressive and inappropriately mount females, regardless of estrus stage.	?
Neurotoxicity	Activation of nNOS augments toxicity by generation of a free radical.	Activation of HO2 protects against toxicity by quenching free radicals.