NDLI: Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ham, Maggie Mizumori, Misa Watanabe, Chikako Wang, Joon-Ho Inoue, Takuya Nakano, Takanari Guth, Paul H. Engel, Eli Kaunitz, Jonathan D. Akiba, Yasutada
Description	Country affiliation: United States Author Affiliation: Ham M ( Department of Medicine, School of Medicine, University of California, Los Angeles, California, USA.)
Abstract	Luminal ATP increases duodenal bicarbonate secretion (DBS) via brush border P2Y receptors. Because ATP is sequentially dephosphorylated to adenosine (ADO) and the brush border highly expresses adenosine deaminase (ADA), we hypothesized that luminal [ADO] regulators and sensors, including P1 receptors, ADA, and nucleoside transporters (NTs) regulate DBS. We measured DBS with pH and CO(2) electrodes, perfusing ADO ± adenosine receptor agonists or antagonists or the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR(inh)-172 on DBS. Furthermore, we examined the effect of inhibitors of ADA or NT on DBS. Perfusion of AMP or ADO (0.1 mM) uniformly increased DBS, whereas inosine had no effect. The A(1/2) receptor agonist 5'-(N-ethylcarboxamido)-adenosine (0.1 mM) increased DBS, whereas ADO-augmented DBS was inhibited by the potent A(2B) receptor antagonist N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]-acetamide (MRS1754) (10 µM). Other selective adenosine receptor agonists or antagonists had no effect. The A(2B) receptor was immunolocalized to the brush border membrane of duodenal villi, whereas the A(2A) receptor was immunolocalized primarily to the vascular endothelium. Furthermore, ADO-induced DBS was enhanced by 2'-deoxycoformycin (1 µM) and formycin B (0.1 mM), but not by S-(4-nitrobenzyl)-6-thioinosine (0.1 mM), and it was abolished by CFTR(inh)-172 pretreatment (1 mg/kg i.p). Moreover, ATP (0.1 mM)-induced DBS was partially reduced by (1R,2S,4S,5S)-4-2-iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (MRS2500) or 8-[4-[4-(4-chlorophenzyl)piperazide-1-sulfonyl)phenyl]]-1-propylxanthine (PSB603) and abolished by both, suggesting that ATP is sequentially degraded to ADO. Luminal ADO stimulates DBS via A(2B) receptors and CFTR. ATP release, ecto-phosphohydrolases, ADA, and concentrative NT may coordinately regulate luminal surface ADO concentration to modulate ADO-P1 receptor signaling in rat duodenum.
File Format	HTM / HTML
ISSN	00223565
e-ISSN	15210103
DOI	10.1124/jpet.110.171520
Journal	Journal of Pharmacology and Experimental Therapeutics
Issue Number	3
Volume Number	335
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2010-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Purinergic P1 Receptor Antagonists Research Support, Non-u.s. Gov't Equilibrative Nucleoside Transport Proteins Bicarbonates Adenosine Triphosphate Adenosine A2 Receptor Antagonists Discipline Pharmacology Antagonists & Inhibitors Receptor, Adenosine A2b Purinergic P2y Receptor Agonists Physiology Adenosine Deaminase Purinergic P1 Receptor Agonists Intestinal Mucosa Adenosine Receptors, Purinergic P1 Duodenum Signal Transduction Secretion Rats, Sprague-dawley Pharmacology Metabolism Adenosine Monophosphate Drug Effects Adenosine A2 Receptor Agonists Membrane Proteins Animals Discipline Therapeutics Perfusion Membrane Transport Proteins
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Neurogenic mucosal bicarbonate secretion in guinea pig duodenum.

Effect of adenosine and some of its structural analogues on the conductance of NMDA receptor channels in a subset of rat neostriatal neurones

Adenosine negatively regulates duodenal motility in mice: role of A(1) and A(2A) receptors.

Evidence for requirement of tyrosine phosphorylation in endothelial P2Y- and P2U- purinoceptor stimulation of prostacyclin release.

Blunted coronary vasodilator response to uridine adenosine tetraphosphate in post-infarct remodeled myocardium is due to reduced P1 receptor activation.

The role of adenosine receptors in the action of theophylline on human peripheral blood mononuclear cells from healthy and asthmatic subjects.

Contractile effects of uridine 5'-triphosphate in the rat duodenum.

Theophylline inhibits the differentiation of human monocyte into dendritic cell potentially via adenosine receptor antagonism

Adenosine monophosphate as a mediator of ATP effects at P1 purinoceptors

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats

Similar Documents

Neurogenic mucosal bicarbonate secretion in guinea pig duodenum.

Effect of adenosine and some of its structural analogues on the conductance of NMDA receptor channels in a subset of rat neostriatal neurones

Adenosine negatively regulates duodenal motility in mice: role of A(1) and A(2A) receptors.

Evidence for requirement of tyrosine phosphorylation in endothelial P2Y- and P2U- purinoceptor stimulation of prostacyclin release.

Blunted coronary vasodilator response to uridine adenosine tetraphosphate in post-infarct remodeled myocardium is due to reduced P1 receptor activation.

The role of adenosine receptors in the action of theophylline on human peripheral blood mononuclear cells from healthy and asthmatic subjects.

Contractile effects of uridine 5'-triphosphate in the rat duodenum.

Theophylline inhibits the differentiation of human monocyte into dendritic cell potentially via adenosine receptor antagonism

Adenosine monophosphate as a mediator of ATP effects at P1 purinoceptors

Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats