Purinergic signalling in the pancreas in health and disease

Abstract

Pancreatic cells contain specialised stores for ATP. Purinergic receptors (P2 and P1) and ecto-nucleotidases are expressed in both endocrine and exocrine calls, as well as in stromal cells. The pancreas, especially the endocrine cells, were an early target for the actions of ATP. After the historical perspective of purinergic signalling in the pancreas, the focus of this review will be the physiological functions of purinergic signalling in the regulation of both endocrine and exocrine pancreas. Next, we will consider possible interaction between purinergic signalling and other regulatory systems and their relation to nutrient homeostasis and cell survival. The pancreas is an organ exhibiting several serious diseases -cystic fibrosis, pancreatitis, pancreatic cancer and diabetes -and some are associated with changes in life-style and are increasing in incidence. There is upcoming evidence for the role of purinergic signalling in the pathophysiology of the pancreas, and the new challenge is to understand how it is integrated with other pathological processes.

Role of vesicular nucleotide transporter VNUT (SLC17A9) in release of ATP from AR42J cells and mouse pancreatic acinar cells

“…These experiments show that VNUT is important for ATP loading into ZG and eventual ATP release, presumably with amylase and other digestive enzymes. Accompanied with fluid secretion originating in acini, this ATP/enzyme mixture is first in contact with luminal membranes of pancreatic ducts, which express various P2 receptors that can initiate and potentiate fluid secretion by pancreatic ducts [1,24,25]. This acini-to-duct purinergic signalling is well established, and the concentration of ATP released into the lumen, estimated to be in high micromolar range by imaging methods, would be sufficient to activate these receptors [4,9].…”

“…Purinergic receptors are well expressed in both endocrine and exocrine pancreas, particularly in β-cells, duct cells, and stellate cells [1]. ATP is released from most cells, and the release mechanism is currently an intensive research field, where the focus is on identifying whether ATP is released via ion channels/ transporters, pannexin or connexins, or via vesicular transport [2,3].…”

The role of P2X7 receptors in tissue fibrosis: a brief review

“…Burnstock and Novak reported the implications of purinergic signaling in chronic pancreatitis (CP) [73]. CP is characterized by inflammatory cell infiltration, progressive organ atrophy, and disorganized collagen deposition [74].…”

Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries

“…There is increasing evidence for the role of purinergic signalling in the pathophysiology of the pancreas [2]. Hence, drugs designed to target specific components of purinergic system may be of relevance to the management of pancreatitis, cystic fibrosis, pancreatic cancer and diabetes.…”

“…Although the exact mechanisms remain to be established, it is generally agreed that an increase in endocrine cell activity during hormone secretion corresponds with an increase in blood flow, to meet metabolic demand. The role of exogenous purine and pyrimidine nucleotides in controlling the functions of endocrine and exocrine components of the pancreas are well described [1,2], but little is known about their effects on pancreatic arterial vasocontractility.…”