ATP Release and Effects in Pancreas

Ivana Novak; Jan Amstrup; Katrine Lütken Henriksen; Susanne Edeling Hede; Christiane E. Sørensen

doi:10.1002/ddr.10192

ATP Release and Effects in Pancreas

Ivana Novak, Jan Amstrup, Katrine Lütken Henriksen, Susanne Edeling Hede, Christiane E. Sørensen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

8 Citationer (Scopus)

Abstract

Udgivelsesdato: May 2003

Originalsprog	Engelsk
Tidsskrift	Drug Development Research
Vol/bind	59
Udgave nummer	1
Sider (fra-til)	128-135
ISSN	0272-4391
DOI	https://doi.org/10.1002/ddr.10192
Status	Udgivet - 2003

Bibliografisk note

Keywords
P2 receptors • luciferin • quinacrine • pancreatic ducts • CLSM

Adgang til dokumentet

10.1002/ddr.10192

Citationsformater

@article{0fe6b9c074c511dbbee902004c4f4f50,

title = "ATP Release and Effects in Pancreas",

abstract = "ATP and other nucleotides are released from various cells, but the pathway and physiological stimulus for ATP release are often unclear. The focus of our studies is the understanding of ATP release and signaling in rat exocrine pancreas. In acinar suspension mechanical stimulation, hypotonic shock and, most importantly, cholinergic stimulation released 5-20nM ATP into the medium, as monitored by luminescence of the luciferin/luciferase reaction. ATP release was visualized at the single acinus level as luciferin consumption detected by confocal laser scanning microscopy (CLSM). The estimated ATP concentrations were higher, about 10µM, around acinar cells after cholinergic stimulation. Fluorescence of quinacrine and MANT-ATP indicated that some ATP is stored in secretory granules. Pancreatic acini have transcripts for P2X1, P2X4, P2Y2, and P2Y4 receptors, but measurements of Ca2+ signals in isolated acini using Fura-2 and CLSM revealed that only about 15% of acini respond to extracellular ATP or UTP. Hence, in acini only a few P2 receptors are functional and the distribution seems heterogenous. In contrast, pancreatic ducts have transcripts for P2Y2, P2Y4, P2X4, and P2X7 receptors that consistently increase intracellular Ca2+. Patch-clamp studies show that P2Y2/P2Y4 receptors inhibit K+ channels, and thus downregulate secretion. P2X4/P2X7 channels stimulate Na+/Ca2+ influx and may upregulate secretion by yet unknown mechanisms. Taken together, our studies show that pancreatic acini release ATP, primarily in response to cholinergic stimulation, and thus ATP may be a paracrine mediator between pancreatic acini and ducts. Drug Dev. Res. 59:128-135, 2003. {\textcopyright} 2003 Wiley-Liss, Inc.",

author = "Ivana Novak and Jan Amstrup and Henriksen, {Katrine L{\"u}tken} and Hede, {Susanne Edeling} and S{\o}rensen, {Christiane E.}",

note = "Keywords P2 receptors • luciferin • quinacrine • pancreatic ducts • CLSM",

year = "2003",

doi = "10.1002/ddr.10192",

language = "English",

volume = "59",

pages = "128--135",

journal = "Drug Development Research",

issn = "0272-4391",

publisher = "JohnWiley & Sons, Inc.",

number = "1",

}

TY - JOUR

T1 - ATP Release and Effects in Pancreas

AU - Novak, Ivana

AU - Amstrup, Jan

AU - Henriksen, Katrine Lütken

AU - Hede, Susanne Edeling

AU - Sørensen, Christiane E.

N1 - Keywords P2 receptors • luciferin • quinacrine • pancreatic ducts • CLSM

PY - 2003

Y1 - 2003

N2 - ATP and other nucleotides are released from various cells, but the pathway and physiological stimulus for ATP release are often unclear. The focus of our studies is the understanding of ATP release and signaling in rat exocrine pancreas. In acinar suspension mechanical stimulation, hypotonic shock and, most importantly, cholinergic stimulation released 5-20nM ATP into the medium, as monitored by luminescence of the luciferin/luciferase reaction. ATP release was visualized at the single acinus level as luciferin consumption detected by confocal laser scanning microscopy (CLSM). The estimated ATP concentrations were higher, about 10µM, around acinar cells after cholinergic stimulation. Fluorescence of quinacrine and MANT-ATP indicated that some ATP is stored in secretory granules. Pancreatic acini have transcripts for P2X1, P2X4, P2Y2, and P2Y4 receptors, but measurements of Ca2+ signals in isolated acini using Fura-2 and CLSM revealed that only about 15% of acini respond to extracellular ATP or UTP. Hence, in acini only a few P2 receptors are functional and the distribution seems heterogenous. In contrast, pancreatic ducts have transcripts for P2Y2, P2Y4, P2X4, and P2X7 receptors that consistently increase intracellular Ca2+. Patch-clamp studies show that P2Y2/P2Y4 receptors inhibit K+ channels, and thus downregulate secretion. P2X4/P2X7 channels stimulate Na+/Ca2+ influx and may upregulate secretion by yet unknown mechanisms. Taken together, our studies show that pancreatic acini release ATP, primarily in response to cholinergic stimulation, and thus ATP may be a paracrine mediator between pancreatic acini and ducts. Drug Dev. Res. 59:128-135, 2003. © 2003 Wiley-Liss, Inc.

AB - ATP and other nucleotides are released from various cells, but the pathway and physiological stimulus for ATP release are often unclear. The focus of our studies is the understanding of ATP release and signaling in rat exocrine pancreas. In acinar suspension mechanical stimulation, hypotonic shock and, most importantly, cholinergic stimulation released 5-20nM ATP into the medium, as monitored by luminescence of the luciferin/luciferase reaction. ATP release was visualized at the single acinus level as luciferin consumption detected by confocal laser scanning microscopy (CLSM). The estimated ATP concentrations were higher, about 10µM, around acinar cells after cholinergic stimulation. Fluorescence of quinacrine and MANT-ATP indicated that some ATP is stored in secretory granules. Pancreatic acini have transcripts for P2X1, P2X4, P2Y2, and P2Y4 receptors, but measurements of Ca2+ signals in isolated acini using Fura-2 and CLSM revealed that only about 15% of acini respond to extracellular ATP or UTP. Hence, in acini only a few P2 receptors are functional and the distribution seems heterogenous. In contrast, pancreatic ducts have transcripts for P2Y2, P2Y4, P2X4, and P2X7 receptors that consistently increase intracellular Ca2+. Patch-clamp studies show that P2Y2/P2Y4 receptors inhibit K+ channels, and thus downregulate secretion. P2X4/P2X7 channels stimulate Na+/Ca2+ influx and may upregulate secretion by yet unknown mechanisms. Taken together, our studies show that pancreatic acini release ATP, primarily in response to cholinergic stimulation, and thus ATP may be a paracrine mediator between pancreatic acini and ducts. Drug Dev. Res. 59:128-135, 2003. © 2003 Wiley-Liss, Inc.

U2 - 10.1002/ddr.10192

DO - 10.1002/ddr.10192

M3 - Journal article

SN - 0272-4391

VL - 59

SP - 128

EP - 135

JO - Drug Development Research

JF - Drug Development Research

IS - 1

ER -