KF24345, an adenosine uptake inhibitor, ameliorates the severity and mortality of lethal acute pancreatitis via endogenous adenosine in mice

Noji, Tohru; Nan-ya, Ken-ichiro; Mizutani, Mirai; Katagiri, Chikako; Sano, Junichi; Takada, Chie; Nishikawa, Satoshi; Karasawa, Akira; Kusaka, Hideaki

doi:10.1016/s0014-2999(02)02476-7

Cited by 23 publications

(12 citation statements)

References 33 publications

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“…Another type of experiment also indicates that adenosine levels may be important. An adenosine uptake inhibitor (KF24345) ameliorated the severity and mortality of lethal acute pancreatitis, and this effect was abolished by pretreatment with an A 2A receptor antagonist (ZM 341385) [158]. Taken together, these results at the organ level indicate that endogenous adenosine might have a cytoprotective role in the pancreas, similar to other organs such as the heart and brain [74,159].…”

Section: Exocrine Pathophysiology and Therapeutic Potentialsmentioning

confidence: 75%

Purinergic receptors in the endocrine and exocrine pancreas

Novak

2007

Purinergic Signalling

115

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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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Section: Exocrine Pathophysiology and Therapeutic Potentialsmentioning

confidence: 75%

Purinergic receptors in the endocrine and exocrine pancreas

Novak

2007

Purinergic Signalling

115

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“…Nevertheless, adenosine may be cytoprotective. Inhibition of adenosine uptake, and stimulation of A 2A receptors, ameliorates caerulein-induced pancreatitis in mice (Noji et al 2002). Recurrent acute and chronic pancreatitis have underlying genetic predilections and a number of genes coding for digestive enzymes and also for CFTR underlie the pathophysiology of pancreatitis (Ooi et al 2010).…”

Section: Pancreatitismentioning

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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“…It is therefore assumed that prevention of adenosine uptake into the cells and its subsequent metabolism can selectively enh ance extracellular concentrations of adenosine at inflamed sites, resulting in an anti-inflammatory effect [57] . Protective or ameliorating effects of adenosine uptake inhibitors in ischemic cardiac and cerebral injury, organ transplantation, seizures, thrombosis, insomnia, pain and inflammatory diseases have been reported [58] . Preclinical and clinical results indicate the possibility of therapeutic application of adenosine uptake inhibitors [58,59] .…”

Section: Roles Of Adenosine Receptors (Ars) and Nucleoside Transportementioning

confidence: 99%

“…Protective or ameliorating effects of adenosine uptake inhibitors in ischemic cardiac and cerebral injury, organ transplantation, seizures, thrombosis, insomnia, pain and inflammatory diseases have been reported [58] . Preclinical and clinical results indicate the possibility of therapeutic application of adenosine uptake inhibitors [58,59] .…”

Section: Roles Of Adenosine Receptors (Ars) and Nucleoside Transportementioning

confidence: 99%

Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation

Liou¹

2010

WJD

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Diabetic retinopathy is a leading cause of blindness among working-age adults. Despite many years of research, treatment options for diabetic retinopathy remain limited and with adverse effects. Discovery of new molecular entities with adequate clinical activity for diabetic retinopathy remains one of the key research priorities in ophthalmology. This review is focused on the therapeutic effects of cannabidiol (CBD), a nonpsychoactive native cannabinoid, as an emerging and novel therapeutic modality in ophthalmology based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy -a retinal disease associated with vascular-neuroinflammation. Special emphasis is placed on novel mechanisms which may shed light on the pharmacological activity associated with CBD preclinically. These include a selfdefence system against inflammation and neurodegeneration mediated by inhibition of equilibrative nucleoside transporter and activation of adenosine receptor by treatment with CBD.

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KF24345, an adenosine uptake inhibitor, ameliorates the severity and mortality of lethal acute pancreatitis via endogenous adenosine in mice

Cited by 23 publications

References 33 publications

Purinergic receptors in the endocrine and exocrine pancreas

Purinergic receptors in the endocrine and exocrine pancreas

Purinergic signalling in the pancreas in health and disease

Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation

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