ATHEROSCLEROSIS in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators1–3—agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor)4. Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium5,6. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties7. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.

Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.

This review will focus on the bioenergetics, mechanism, and molecular basis of neurotransmitter transport. As indicated in the next section, these processes play an important role in the overall process of synaptic transmission. During the last few years, direct evidence has been obtained that these processes are coupled chemiosmotically, i.e., the accumulation of neurotransmitters is driven by ion gradients. Two types of neurotransmitter transport systems have been identified: sodium-coupled systems located in the synaptic plasma membrane of nerves (and sometimes in the plasma membrane of glial cells) and proton-coupled systems which are part of the membrane of intracellular storage organelles. From a bioenergetic point of view, the sodium-coupled systems are especially interesting, since it has recently been discovered that many systems require other ions in addition to sodium. It has now been demonstrated in several cases that, besides sodium ions, these additional ions, such as chloride and potassium, serve as additional coupling ions. These systems will be reviewed here in considerable detail with emphasis on the role of the additional ions. In the second part of the review we shall focus on neurotransmitter transport into storage organelles. Although both sodium and proton coupled systems have been reviewed in the past, there has been a shift from a kinetic and thermodynamic to a biochemical approach. In fact, a few transporters have been identified and functionally reconstituted. These developments have of course been incorporated in this review.

Mechanism of transport and storage of neurotransmitters.

Rapid separation of low molecular weight solutes from liposomes without dilution.

Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes.

Control, Modulation, and regulation of cell calcium.

Transport of glycine by hemolyzed and restored pigeon red blood cells. Symmetry properties, trans effects of sodium ion and glycine, and their description by a single rate equation.

Anion effects on glycine entry into pigeon red blood cells

Evidence that lysolecithin is an important causal agent of atherosclerosis.

A sephadex column procedure for measuring uptake and loss of low molecular weight solutes from small, lipid-rich vesicles

The effect of gramicidin on sodium-dependent accumulation of glycine by pigeon red cells: A test of the cation gradient hypothesis

George A. Vidaver

Papers

Transport of glycine by hemolyzed and restored pigeon red blood cells. Symmetry properties, trans effects of sodium ion and glycine, and their description by a single rate equation.

Anion effects on glycine entry into pigeon red blood cells

Evidence that lysolecithin is an important causal agent of atherosclerosis.

A sephadex column procedure for measuring uptake and loss of low molecular weight solutes from small, lipid-rich vesicles

The effect of gramicidin on sodium-dependent accumulation of glycine by pigeon red cells: A test of the cation gradient hypothesis