Purinergic Signalling in Pancreatic Islet Endothelial Cells - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 209

are present on different types of vascular cells. The endothelial cells have high
expression of P2Y 1 , P2Y 2 and P2X 4 receptors, medium expression of P2Y 6 recep-
tors and possible expression of P2Y 11 receptors [11]. Also vascular smooth muscle
cells (VSM), and adventitial cells, have purinergic receptors that enable purines and
pyrimidines to induce contraction or dilation of VSM [24, 64].
External ATP has organ-specific effects on vascular endothelium. In the present
review evidence is presented that purinoceptor-mediated interactions between islet
capillaries and endocrine cells are key factors for coordinating glucose metabolism
of the

β

-cells with blood flow responses and insulin release. Recent findings
emphasize the importance of the islet microvasculature for the functions of this
highly complex micro-organ, which crucially depends on ATP as a signalling
molecule [37].

12.2 ATP and Vascular Endothelium

12.2.1 General Aspects on Vascular ATP Signalling

External ATP affects the vascular tone through several mechanisms. Released as
a co-transmitter from perivascular sympathetic nerves ATP acts on P2 receptors
causing VSM contraction [12]. ATP can also be released from endothelial cells
during changes in blood flow (mainly increased shear stress) or hypoxia to act on
endothelial P2X and P2Y receptors which results in release of nitric oxide (NO)
with vasodilation [11, 86]. A third possibility for ATP to affect local circulation
is release of purines from erythrocytes and granulocytes [23]. Local production of
ecto-nucleotidases helps to modulate the effects of ATP [87]. These mechanisms
will be discussed further below with special emphasis on islet endothelium.
In addition to controlling the vascular tone, external ATP and its degradation
products have important long-term actions on endothelial and smooth muscle cell
proliferation, differentiation, and death [10, 24, 26]. Recent studies on islet vascula-
ture suggest that interactions between endocrine cells, nerves and endothelial cells
may be important for the phenotype properties of parenchyme cells [47, 48, 55].

12.2.2 External ATP Generates and Propagates Ca 2+ Signals
in Microvascular Endothelium

The responses of microvascular endothelial cells are highly heterogenous in space
and time [56]. Thus, there are functional differences not only between endothelium
from large blood vessels and microvascular endothelium, but also with regard to the
organs involved. All types of microvascular endothelial cells studied so far respond
to ATP with increase of [Ca 2+ ] i [20, 83]. The elevation of [Ca 2+ ] i is known to initiate
a number of processes [83], including release of vasoactive NO, endothelium-
derived hyperpolarizing factor (EDHF) and prostacyclin [6, 57, 81]. Constitutive