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Interactions Between Cholinergic and Prostaglandin Signaling Elements in the Urothelium: Role for Muscarinic Type 2 Receptors.

Lookup NU author(s): Dr Christopher NileORCiD, Professor James Gillespie


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OBJECTIVE To characterize the interactions between the cholinergic and prostaglandin signaling systems within the urothelium-lamina propria of the guinea pig and elucidate the role of muscarinic receptors in these interactions. METHODS The urothelium-lamina propria was isolated from guinea pig bladders, cut into strips (5 x 10 mm), and maintained in vitro. The tissue was either stretched or left unstretched but exposed to 2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate tri(triethylammonium) salt, arecaidine, and prostaglandin E-2 (PGE(2)). Acetylcholine and PGE(2) release was measured using a GeneBLAzer M-3 CHOK1-bla cell reporter assay and an enzyme immunoassay, respectively. The role of the muscarinic type 2 and 3 (M-2 and M-3, respectively) receptors and nitric oxide in mediating PGE(2) release was determined in the presence of the muscarinic antagonists 11-[(2-[(diethylamino) methyl]-1-piperidinyl)acetyl]-5,11-dihydro-6H-pyrido[2,3b][1,4] benzodiazepin-6-one and darafenicin and a nitric oxide donor (NONOate). RESULTS Acetylcholine release was detected in response to stretch and in the unstretched preparations exposed to PGE(2) or the adenosine triphosphate analog 2'(3')-O-(4-benzoylbenzoyl) adenosine-5'-triphosphate tri(triethylammonium) salt. The cholinergic agonist arecaidine induced a concentration-dependent production of PGE(2) (half-maximal concentration 75 nM). The arecaidine stimulation of PGE(2) production was inhibited in a dose-dependent manner by the antagonist AFDX-116 (M-2 > M-3; half-maximal inhibition 110 nM) but not darifenacin (M-2 > > M-3). Finally, in the presence of the nitric oxide donor, NONOate, arecaidine-stimulated PGE(2) production was inhibited. CONCLUSION These observations demonstrate that complex signal interactions occur within the urothelium involving acetylcholine, adenosine triphosphate, nitric oxide, and PGE(2). In addition, the data have demonstrated a role for muscarinic M-2 receptors and nitric oxide in the cholinergic regulation of PGE(2) production in the bladder wall. UROLOGY 79: 240.e17-240.e23, 2012. (C) 2012 Elsevier Inc.

Publication metadata

Author(s): Nile CJ, Gillespie JI

Publication type: Article

Publication status: Published

Journal: Urology

Year: 2012

Volume: 79

Issue: 1

Pages: 240.e17–240.e23

Print publication date: 04/11/2011

ISSN (print): 0090-4295

ISSN (electronic): 1527-9995

Publisher: Excerpta Medica, Inc.


DOI: 10.1016/j.urology.2011.08.029

PubMed id: 22055690


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