Number 22, 2004
Endothelial Dysfunction

Glossary

5-HT(1D)-serotonin receptor
Serotonin (5-hydroxytryptamine or 5-HT) is a transmitter in the central nervous system, and also functions in the periphery as a ubiquitous hormone involved in vasocontriction and platelet function. Serotonin acts on a variety of serotonin receptors, one of these being the 5-HT1D receptors.

Autacoids
Autacoids are organic substances produced in one cell type that act either on the same cell, or a cell nearby to produce a biological effect. Nitric oxide (NO) or prostaglandins are examples of autacoids.

Calmodulin
Calmodulin is an important molecule that binds calcium and stimulates the activity of calmodulin-dependent kinases. Calmodulin mediates many important reactions in the cell, including excitation contraction coupling of muscle cells.

Caveolin
Caveolie are invaginations in the plasma membrane of cells that represent subcompartments of the plasma membrane. Caveolins are caveolie coat proteins. Recent interest has focussed on the role of G-proteins associated with caveolins as a mechanism for transmembrane signalling.

Cyclic GMP
Cyclic guanylate monophosphate (cyclic GMP) is produced from guanylate triphosphate (GTP) via the enzyme guanylate cyclase. Cyclic GMP has numerous actions as an intracellular signalling molecule, including relaxation of smooth muscle. The vasodilatory effect of NO on smooth muscle is mediated by the production of cyclic GMP by guanylate cyclase.

Epoxyeicosatrienoic acids
Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. The EETs have diverse actions, including somatostatin, insulin and glucagon release from the pancreas. They also modulate ion transport and gene expression, producing vasorelaxation, as well as anti-inflammatory and pro-fibrinolytic effects.

G-proteins
G-proteins refer to a group of guanylate triphosphate (GTP) binding proteins that are crucial in linking numerous types of receptor to their subcellular signalling pathways. An example of this is the x-adrenergic receptor, which is coupled to adenylate cyclase via a G-protein. Receptors that are coupled to the G-protein family are called G-protein coupled receptors.

Geranylgeranyl-pyrophosphate
Geranylgeranyl pyrophosphate (GGPP) is an isoprenoid that is a precursor for numerous molecules essential for cellular function. GGPP also acts as a substrate in isoprenylation reactions. GGPP is produced from farnesyl-PP, which is produced from geranyl-PP, an intermediate in the cholesterol synthetic pathway. Inhibition of GGPP production, using a geranylgernayl transferase inhibitor can inhibit vascular smooth muscle proliferation. A similar effect can be observed by HMG-CoA reductase inhibition, which inhibits the production of mevalonate, which eventually can go on to produce geranyl-PP.

Hydrobiopterin
Tetra-hydrobiopterin is produced by the reduction of dihydrobiopterin, catalyzed by the enzyme, dihydrofolate reductase. Tetra-hydrobiopterin is an essential cofactor for nitric oxide (NO) formation.

L-arginine
L-arginine is an amino acid. An important function of L-arginine is as a substrate for nitric oxide synthase, which produces nitric oxide (NO). NO is a potent vasodilator of smooth muscle.

Proteins of the Rho-family
The Rho-family of proteins are proteins involved in cellular signalling. An example of this is Rho A, which is involved in vascular smooth muscle proliferation. Platelet-derived growth factor can increase Rho A protein. Rho kinase plays an important role in this process as an effector of Rho A. The RhoA/Rho kinase pathway can mediate calcium sensitization in vascular smooth muscle.

Substance P
Substance P is a tachykinin and physiologically acts as a neurotransmitter and neuromodulator in the nervous system. Pathologically, it can also trigger malignant cells to release cytokines and increase cell proliferation rates.

Thromboxane A2
Thromboxane A₂ is a product of the cycloxygenase pathway of arachidonic acid metabolism. The production of PGH2 from arachidonic acids by cycloxygenase can be used for a number of different eicosanoid products, including the production of prostaglandins. Metabolism of PGH2 by thromboxane synthase, which is abundant in lung and platelets, results in the production of thromboxane A₂. Thromboxane A₂ has a variety of biological effects, including vasoconstriction and promotion of platelet aggregation.