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Introduction

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High-Yield Terms

  • Endothelium-derived relaxing factor (EDRF): produced and released by vascular endothelium to promote smooth muscle relaxation; was found to be nitric oxide, NO

  • Catecholamines: neurotransmitter family derived from tyrosine, a catechol is an organic compound composed of a benzene ring and at least 2 hydroxyl groups attached, hence the derivation of the name of these compounds

  • Norepinephrine (noradrenaline): principal catecholamine neurotransmitter of sympathetic postganglionic nerves, its actions are exerted by binding to receptors of the adrenergic family

  • Epinephrine (adrenaline): a catecholamine neurotransmitter and hormone that modulates numerous function in the body by binding to receptors of the adrenergic family

  • Dopamine: a catecholamine neurotransmitter that plays a major role in the reward-driven learning processes in the CNS, functions by binding dopaminergic receptors

  • Glutathione: a tripeptide composed of glutamate, cysteine, and glycine that serves as a critical biological reductant; it is also conjugated to drugs to make them more water soluble and is involved in amino acid transport across cell membranes

  • Polyamine: any of a family of organic compounds having 2 or more primary amino groups (–NH2), biologically important polyamines are involved in DNA replication, ion channel modulation, and blood-brain barrier permeability

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Several amino acids possess distinct biochemical functions unrelated to their roles in protein synthesis and as sources of oxidizable carbon. Numerous biologically active compounds are derived from the amino acids such as signaling molecules and neurotransmitters.

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Nitric Oxide Synthesis and Function

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Vasodilators, such bradykinin, do not exert their effects upon the vascular smooth muscle cell in the absence of the overlying endothelium. For example, when bradykinin binds to bradykinin B2 receptors on the surface of endothelial cells, a signal cascade, coupled to the activation phospholipase Cβ (PLCβ), is initiated. The PLCβ-mediated release of inositol trisphosphate, IP3 (from membrane-associated phosphatidylinositol-4,5-bisphosphate, PIP2), leads to the release of intracellular stores of Ca2+. In turn, the elevation in Ca2+ leads to the liberation of endothelium-derived relaxing factor (EDRF) which then diffuses into the adjacent smooth muscle. EDRF was found to be the free radical diatomic gas, NO. NO is formed by the action of NO synthase (NOS) on the amino acid arginine (Figure 31-1).

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FIGURE 31-1:

The reaction catalyzed by nitric oxide synthase. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper's Illustrated Biochemistry, 29th ed. New York: McGraw-Hill; 2012.

Graphic Jump Location
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NO can also be formed from nitrite, derived from vasodilator drugs such as glycerin trinitrate (nitroglycerin) during their metabolism. The half-life of NO is extremely short, lasting only 2-4 seconds. This is because it is a highly reactive free radical and interacts with oxygen and superoxide. NO is inhibited by hemoglobin and other heme proteins which bind it tightly.

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Within smooth muscle cells, NO reacts with the heme moiety ...

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