¿Son todas las partículas de lipoproteínas de alta densidad iguales? / Are all high-density lipoprotein particles equal?

El análisis de las modificaciones de genes que influencian el metabolismo y la función de las lipoproteínas de alta densidad (HDL) en modelos murinos, demuestra que los cambios (aumentos o disminución) de colesterol unido a HDL no son un predictor adecuado de la susceptibilidad a la arteriosclerosis de éstos. Por tanto, los diferentes tipos de partículas de HDL generados por intervención sobre distintas potenciales dianas terapéuticas no son iguales en cuanto a su potencial antiaterogénico. El análisis del transporte reverso de colesterol específico de macrófagos, y de la capacidad de las HDL de proteger frente a la modificación oxidativa de lipoproteínas de baja densidad, aporta una mejor predicción del efecto de la modificación genética efectuada sobre la susceptibilidad a la arteriosclerosis (AU)

Analysis of the genetic modifications that influence high-density lipoprotein (HDL) metabolism and function in murine models shows that changes (whether increases or decreases) in HDL-cholesterol do not accurately predict susceptibility to arteriosclerosis in these models. Therefore, the distinct types of HDL particles generated by interventions on the various potential therapeutic targets differ in their antiatherogenic potential. Analysis of macrophage-specific reverse cholesterol transport and the ability of HDL to protect LDL against oxidative modification is better able to predict the effect of genetic modification on susceptibility to arteriosclerosis (AU)

[ATP as a neurotransmitter in the brain: its possibility based upon recent findings].

We discuss here possible neurotransmitter roles of extracellular ATP in the central nervous system. Important findings concerning the effects of ATP on central neurons have been made in the last few years. A fast neurotransmitter role of ATP in rat medial habenula reported by Edwards et al (1992) may be the best example. In rat cultured hippocampal neurons, we have found that ATP evokes postsynaptic currents, and increases the intracellular Ca2+ concentration. In addition, ATP also produces a "long-term potentiation like effect" in these cells. Receptors for ATP are generally divided into two classes: one class is coupled with ion channels and the other class is coupled with GTP-binding proteins. In cultured hippocampal neurons, the GTP-binding protein-coupled receptors are present and promote the inhibition of K+ channels. Although the channel-coupled receptors have not been identified in the hippocampal neurons, these channels have been found in nucleus solitarii and locus coeruleus. Several types of ATP receptors have been cloned very recently. These cloned receptors, combined with molecular biological techniques, will allow great progress in this field.

Recent developments in the classification and functional significance of receptors for ATP and UTP, evidence for nucleotide receptors.

The presence of a nucleotide receptor activated with similar potencies by UTP and ATP is suggested by recent data from a variety of different cell types. This receptor type appears distinct from previously described ATP-sensitive P2-purinoceptor subtypes and, probably, from other UTP-sensitive receptors, however further studies using selective antagonists are necessary to provide a definitive characterisation. Although the functional role of endogenous extracellular ATP has already achieved recognition there are also many diverse examples of cells and tissues which respond to UTP at micromolar or sub-micromolar concentrations. Therefore, the possible physiological importance of UTP is a fertile area for further investigation. The functional significance of ATP/UTP receptors is underlined by recent demonstrations that UTP and ATP modulate chloride ion secretion in human airways epithelium, possibly by activation of a nucleotide receptor, an effect which may have potential clinical utility in the treatment of cystic fibrosis.