Nitric oxide (NO) and carbon monoxide (CO) are gaseous, labile neurotransmitters that play critical roles in the nervous system. NO is synthesized by nitric oxide synthase (NOS) from L-arginine and diffuses across cell membranes, acting as a neurotransmitter and neuromodulator. It functions by forming covalent bonds with various targets, including enzymes like guanylyl cyclase, and is involved in synaptic transmission, neurotransmission, and blood vessel dilation. NO is also implicated in neurotoxicity, particularly under conditions of excessive production, such as in focal ischemia and neurodegenerative diseases. CO, produced by heme oxygenase (HO), is another gaseous neurotransmitter that binds to heme in guanylate cyclase to activate cGMP. It is involved in various physiological functions, including maintaining endogenous cGMP levels in olfactory neurons and regulating chemosensory responses in the carotid body. Both NO and CO have complex roles in the brain, influencing synaptic transmission, neuroprotection, and neurotoxicity, and their functions are regulated by various molecular mechanisms, including phosphorylation and enzyme activity.Nitric oxide (NO) and carbon monoxide (CO) are gaseous, labile neurotransmitters that play critical roles in the nervous system. NO is synthesized by nitric oxide synthase (NOS) from L-arginine and diffuses across cell membranes, acting as a neurotransmitter and neuromodulator. It functions by forming covalent bonds with various targets, including enzymes like guanylyl cyclase, and is involved in synaptic transmission, neurotransmission, and blood vessel dilation. NO is also implicated in neurotoxicity, particularly under conditions of excessive production, such as in focal ischemia and neurodegenerative diseases. CO, produced by heme oxygenase (HO), is another gaseous neurotransmitter that binds to heme in guanylate cyclase to activate cGMP. It is involved in various physiological functions, including maintaining endogenous cGMP levels in olfactory neurons and regulating chemosensory responses in the carotid body. Both NO and CO have complex roles in the brain, influencing synaptic transmission, neuroprotection, and neurotoxicity, and their functions are regulated by various molecular mechanisms, including phosphorylation and enzyme activity.