Purinergic receptors in the endocrine and exocrine pancreas

Abstract

The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly, these processes have been viewed separately. In β cells, stimulation of P2Y 1 receptors amplifies secretion of insulin in the presence of glucose. Nucleotides released from secretory granules could also contribute to autocrine/paracrine regulation in pancreatic islets. In addition to P2Y 1 receptors, there is also evidence for other P2 and adenosine receptors in β cells (P2Y 2 , P2Y 4 , P2Y 6 , P2X subtypes and A 1 receptors) and in glucagon-secreting α cells (P2X 7 , A 2 receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors are prominent in pancreatic ducts, and several studies indicate that P2Y 2 , P2Y 4 , P2Y 11 , P2X 4 and P2X 7 receptors could regulate secretion, primarily by affecting Cl − and K + channels and intracellular Ca 2+ signalling. In order to understand the physiology of the whole organ, it is necessary to consider the full complement of purinergic receptors on different cells as well as the structural and functional relation between various cells within the whole organ. In addition to the possible physiological function of purinergic receptors, this review analyses whether the receptors could be potential therapeutic targets for drug design aimed at treatment of pancreatic diseases.

Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival

“…Across all tissues, the pancreas is the most active in protein synthesis, with over 90% of the newly synthesized proteins being targeted to the secretory pathway (52). In response to food intake, acinar cells secrete a large amount of pancreatic juice containing electrolytes and a variety of digestive enzymes, including pancreatic lipase and α-amylase (53,54). It is thus well established that ER homeostasis is critical for pancreatic function.…”

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].…”

“…Rat acinar cell line AR42J (CRL-1492, ATCC, passages [15][16][17][18][19][20][21][22][23][24][25] was cultured in RPMI media supplemented with 10 % fetal bovine serum (FBS) and penicillin/streptomycin. Cells were cultured in humidified incubators at 37°C, with 5 % CO 2 in air.…”

Neuroprotective roles of the P2Y2 receptor

“…Purinergic receptors are expressed in many mammalian cell types and are activated by extracellular adenine and uridine nucleotides or nucleosides [6,[29][30][31]. Both P1 receptors for adenosine and P2 receptors (P2Rs) for adenine and/or uridine nucleotides are expressed in cells comprising the CNS and have been shown to regulate important physiological and pathophysiological functions, including neurotransmission, inflammation, cell growth, and apoptosis [11,[31][32][33].…”