Purinergic and Pyriminergic Activation of the Endothelium in Regulation of Tissue Perfusion - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 1

Chapter 1
Purinergic and Pyriminergic Activation
of the Endothelium in Regulation of Tissue
Perfusion

David Erlinge

Abstract The nucleotides ATP, ADP, UTP and UDP acting on P2 receptors
stimulate endothelium dependent dilatation mediated via nitric oxide, endothelium
derived hyperpolarising factors, and prostacyclins (to a lesser extent). They are cru-
cial for shear stress-mediated increases in blood flow and for the increase of tissue
perfusion during exercise and hypoxia. The endothelium can also release potent
contractile tetraphosphate nucleotides (AP 4 A and UP 4 A). The purinergic signal-
ing has been implicated in blood pressure regulation, development of myocardial
infarction, heart failure, pulmonary hypertension, circulatory shock and regulation
of blood flow in most organs of the body. Purinergic and pyriminergic endothelium-
mediated effects are important for physiological and patophysiological regulation
of tissue perfusion.

Keywords Endothelium · ATP · UTP · ADP · UDP · Nitric

oxide · EDHF · AP4A · UP4A · Red blood cell · Spreading dilata-

tion · Vasodilatation · Vasoconstriction · Ectonucleotidase · Hypertension · Conge

stive heart failure · Reactive hyperemia · Pulmonary hypertension · Hypoxia

1.1 Introduction

Effects purines on tissue perfusion were recognized already in 1929 by Drury and
Szent-Györgyi [25]. Since then, it has become increasingly clear that, in addition
to functioning as an intracellular energy source, as DNA or RNA, the purines and
pyrimidines ATP, ADP, UTP and UDP can serve as important extracellular signaling
molecules acting on fifteen P2 receptor subtypes [9, 11, 16, 19, 52]. To terminate
signaling, ectonucleotidases present in the circulation and on cell surfaces, rapidly

B

D. Erlinge ( )

Department of Cardiology, Lund University Hospital, SE-22185 Lund, Sweden
e-mail: [e-mail]