### A. Overview

Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface receptors termed purine receptors. In this review particular emphasis is placed on the discrepancy between the

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Receptors for Purines and Pyrimidines

HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P3 (also known as LPB3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P3-deficient mice, Akt phosphorylation and Ca2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P3-mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.

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HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3

The role of ATP as an extracellular signalling molecule is now well established and evidence is accumulating that ATP and other nucleotides (ADP, UTP and UDP) play important roles in cardiovascular physiology and pathophysiology, acting via P2X (ion channel) and P2Y (G protein-coupled) receptors. In this article we consider the dual role of ATP in regulation of vascular tone, released as a cotransmitter from sympathetic nerves or released in the vascular lumen in response to changes in blood flow and hypoxia. Further, purinergic long-term trophic and inflammatory signalling is described in cell proliferation, differentiation, migration and death in angiogenesis, vascular remodelling, restenosis and atherosclerosis. The effects on haemostasis and cardiac regulation is reviewed. The involvement of ATP in vascular diseases such as thrombosis, hypertension and diabetes will also be discussed, as well as various heart conditions. The purinergic system may be of similar importance as the sympathetic and renin-angiotensin-aldosterone systems in cardiovascular regulation and pathophysiology. The extracellular nucleotides and their cardiovascular P2 receptors are now entering the phase of clinical development.

https://link.springer.com/content/pdf/10.1007%2Fs11302-007-9078-7.pdf

P2 receptors in cardiovascular regulation and disease

The present article is a survey of ESI and MALDI mass spectrometric analysis of nucleic acid oligomers and polymers. In order to limit the extent of the review, mass spectrometry of mononucleotides is generally not considered, except where such data are important for an understanding of the analysis of larger nucleic acids. The first part of the review is a condensed description of the structure and the acid-base properties of nucleic acids. The remaining part is divided into three main sections, dealing with the practical aspects of the two ionization techniques, fragmentation, and applications, respectively. The first section includes an extensive discussion of experimental parameters and problems, which are important for the analysis of different types of nucleic acid samples, including noncovalent complexes and mixtures. At the end of this section, as well as the following one, a comparison between MALDI and ESI as ionization techniques for nucleic acid is given. In addition to a detailed discussion of ion fragmentation, the fragmentation section includes an overview of the direct mass spectrometric sequencing of nucleic acids performed with either technique. The fragmentation reactions occurring upon MALDI and ESI are compared. The last section describes the life science applications of ESI-MS and MALDI-MS of nucleic acids; an account of experiments demonstrating the potential of a method, and of the bona fide solving of problems by ESI and MALDI is given. © 1997 John Wiley & Sons, Inc.

Mass spectrometry of nucleic acids.

The regulation of vascular function by p2 receptors : multiple sites and multiple receptors

OUR understanding of the regulation of vascular tone has been extended since the identification of vasoactive agents such as the atrial natriuretic peptides1, endothelial-derived relaxing factor2 and endothelin3. Unidentified vasopressive agents have been found in platelets4. Here we isolate these vasopressors and identify them as diadenosine pentaphosphate (AP5A) and diadenosine hex-aphosphate (AP6A) by chromatography, mass spectrometry, ultraviolet spectroscopy and enzymatic cleavage. In the vasculature of isolated perfused rat kidney, both diadenosine phosphates were active at a concentration of 10−9 M; in aortic rings, contractions were elicited at 10−8 M.Intra-aortic injection in the rat caused a prolonged increase in blood pressure. We conclude that AP5A and AP6A may play a part in local vasoregulation and possibly in the regulation of blood pressure.

Gitte Brüggemann

Papers

Diadenosine phosphates and the physiological control of blood pressure