Adenosine potentiates secretin-stimulated pancreatic exocrine secretion in the dog

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.

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“…In the intact dog pancreas adenosine modulated secretion evoked by secretin [136,137]. Since the effects could also be systemic, e.g.…”

Section: Pancreatic Acinimentioning

confidence: 99%

Purinergic receptors in the endocrine and exocrine pancreas

Novak

2007

Purinergic Signalling

115

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“…Using agonists and antagonists for adenosine receptors, it was implicated that A 2A receptors were involved in HCO À 3 secretory response [16]. Nevertheless, as the effects could also be systemic, e.g., by effecting blood flow [39] or indirectly mediated by pancreatic hormones [25], it is not easy to conclude whether adenosine effect was exerted on pancreatic ducts and which adenosine receptors were affected.…”

Section: Introductionmentioning

confidence: 97%

“…Indeed, adenosine response was not found on isolated rat acini. In intact dog pancreas, adenosine modulated secretion evoked by secretin [39,40]. Using agonists and antagonists for adenosine receptors, it was implicated that A 2A receptors were involved in HCO À 3 secretory response [16].…”

Section: Introductionmentioning

confidence: 99%

Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport

Novak

Hede

Hansen

2007

Pflugers Arch - Eur J Physiol

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Previously, we have shown that pancreatic acini release adenosine triphosphate (ATP) and ATP-handling enzymes, and pancreatic ducts express various purinergic P2 receptors. The aim of the present study was to establish whether pancreatic ducts also express adenosine receptors and whether these could be involved in secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR) Cl- channels or Ca2+-activated Cl- channels and H(+)/HCO(-)(3) transporters. Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts and human duct cell adenocarcinoma lines showed that they express A1, A2A, A2B, and A3 receptors. Real-time PCR revealed relatively low messenger RNA levels of adenosine receptors compared to beta-actin; the rank order for the receptors was A2A>A2B>or=A3>>A1 for rat pancreas and A2B>A2A>>A3>or=A1 for duct cell lines. Whole-cell patch-clamp recordings on rat pancreatic ducts showed that, in about half of the recordings, adenosine depolarized the membrane voltage, and this was because of the opening of Cl- channels. Using a Cl--sensitive fluorophore and single-cell imaging on duct cell lines, it was found that 58% of PANC-1 cells responded to adenosine, whereas only 9% of CFPAC-1 cells responded. Adenosine elicited Ca2+ signals only in a few rat and human duct cells, which did not seem to correlate with Cl- signals. A2A receptors were localized in the luminal membranes of rat pancreatic ducts, plasma membrane of many PANC-1 cells, but only a few CFPAC-1 cells. Taken together, our data indicate that A2A receptors open Cl- channels in pancreatic ducts cells with functional CFTR. We propose that adenosine can stimulate pancreatic secretion and, thereby, is an active player in the acini-to-duct signaling.

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“…This finding supports nicely earlier studies performed on dog whole pancreas. Although adenosine decreased blood flow, it enhanced secretinstimulated HCO K 3 and fluid secretion (Yamagishi et al 1985(Yamagishi et al , 1986. A pharmacological study indicated that it was the A 2A adenosine receptor that was involved in this secretory response in dog pancreas (Iwatsuki 2000).…”

Section: Pancreatic Ductsmentioning

confidence: 99%

“…Adenosine receptors, probably A 2A , mediate vasorelaxation in the pancreatic vascular bed (Yamagishi et al 1985, Laurent et al 1999. Adenosine may be protective in pancreatitis (see below) and as indicated by the following experiments.…”

Section: Pancreatic Vasculaturementioning

confidence: 99%

Purinergic signalling in the pancreas in health and disease

Burnstock

Novak²

2012

Journal of Endocrinology

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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.

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Adenosine potentiates secretin-stimulated pancreatic exocrine secretion in the dog

Cited by 16 publications

References 15 publications

Purinergic receptors in the endocrine and exocrine pancreas

Purinergic receptors in the endocrine and exocrine pancreas

Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport

Purinergic signalling in the pancreas in health and disease

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