Biology Reference
In-Depth Information
nitric oxide synthase, activated by the Ca
2+
-calmodulin complex [57], is present in
islet capillaries and an essential regulator islet blood flow [80]. ATP is a secretory
product of endothelium. Indeed, regenerative release of ATP is known to propagate
stimulatory Ca
2+
signals between the endothelial cells [13, 40]. The observation that
external ATP induces oscillatory [Ca
2+
]
i
in capillaries and arterioles adds further
weight to the argument that microvascular endothelium has a synchronizing effect
on adjacent cells. Changes in endothelial [Ca
2+
]
i
have profound effects on release of
vasoactive substances, and consequently on regional microcirculation. As referred
to below addition of ATP increases [Ca
2+
]
i
in the pancreatic islet endothelium.
12.3 ATP and the Pancreas
12.3.1 Purinergic Nerves and Pancreas
Pancreatic exocrine secretion is regulated both by neural and hormonal factors,
including external ATP [66, 68]. Moreover, multiple functional P2X and P2Y recep-
tors have been identified in pancreatic duct cells [58, 68] and found to modify the
exocrine pancreatic secretion. It is not yet clear whether the nucleotides are exerting
their effects through autocrine, paracrine, or neuronal mechanisms. The pancreatic
islets possess a rich innervation, which comprises parasympathetic, sympathetic,
purinergic as well as sensory nerves [1, 74]. It has been suggested that islets consti-
tute paraneurons ensheathed in Schwann cells [82]. The various types of islet nerves
are known to modulate the hormone secretion and blood perfusion of the islets.
12.3.2 Effects of ATP and Adenosine on Exocrine Pancreatic
Arterioles
Measurement of pressure during perfusion of the isolated rat pancreas made it pos-
sible to assess the vascular dilation or constriction in the arterioles. Using this
approach it was found that the effect of ATP reflected the balance between P2Y-
receptor mediated vasodilation and P2X-mediated vasoconstriction [39]. On the
other hand adenosine was found to be an unequivocal dilator of arterioles in the
exocrine pancreas [4, 17].
12.3.3 Anatomy of the Pancreatic Islets
Pancreatic islets consist of different types of cells located in aggregates of
varying sizes with a diameter up to 400
μ
m. In the human pancreas there is
10
6
1-2
×
islets containing insulin-producing
β
-cells and to a lesser extent of
glucagon-producing
-cells. All islets pos-
sess a dense vascular network with fenestrated capillaries [72]. Each
α
-cells and somatostatin-producing
δ
β
-cell,
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