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ATP Induces Guinea Pig Gallbladder Smooth Muscle Excitability via the P2Y4 Receptor and COX-1 Activity

Bartoo AC, Nelson MT, Mawe GM

American Journal of Physiology: Gastrointestinal and Liver Physiology (Print). 2008;294(6):G1362-G1368.

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Abstract

The purpose of this study was to elucidate the mechanisms by which ATP increases guinea pig gallbladder smooth muscle (GBSM) excitability. We evaluated changes in membrane potential and action potential (AP) frequency in GBSM by use of intracellular recording. Application of ATP (100 microM) caused membrane depolarization and a significant increase in AP frequency that were not sensitive to block by tetrodotoxin (0.5 microM). The nonselective P2 antagonist, suramin (100 microM), blocked the excitatory response, resulting in decreased AP frequency in the presence of ATP. The excitatory response to ATP was not altered by pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (30 microM), a nonselective P2X antagonist. UTP also caused membrane depolarization and increased AP frequency, with a similar dose-response relationship as ATP. RT-PCR demonstrated that the P2Y(4), but not P2Y(2), receptor subtype is expressed in guinea pig gallbladder muscularis. ATP induced excitation was blocked by indomethacin (10 microM) and the cyclooxygenase (COX)-1 inhibitor SC-560 (300 nM), but not the COX-2 inhibitor nimesulide (500 nM). These data suggest that ATP stimulates P2Y(4) receptors within the gallbladder muscularis and, in turn, stimulate prostanoid production via COX-1 leading to increased excitability of GBSM.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Publication type:
Published date:
Language:
eng
Abbreviated journal title:
ISSN:
Volume:
294
Issue:
6
Start page:
G1362-G1368
Digital Object Identifier:
10.1152/ajgi.00043.2008
Attached files embargo period:
Immediate release
Attached files release date:
30th September, 2014
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:235612
Created by:
Nelson, Mark
Created:
30th September, 2014, 20:04:27
Last modified by:
Nelson, Mark
Last modified:
30th September, 2014, 20:04:27

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