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Endothelium-derived NO is formed in response to stimulation of the endothelial cells by cholinergic nerves. Acetylcholine causes the production of inositol triphosphate (IP3), an important second messenger in many hormone signal transduction pathways. IP3 opens calcium channels in the endoplasmic membrane of the endothelial cells; the liberated calcium then activates NO synthase and causes the production of NO.

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