Interactions between cholinergic and prostaglandin signaling elements in the urothelium: Role for muscarinic type 2 receptors

Nile, C.J. and Gillespie, J.I. (2012) Interactions between cholinergic and prostaglandin signaling elements in the urothelium: Role for muscarinic type 2 receptors. Urology, 79(1), 240.e17-240.e23. (doi: 10.1016/j.urology.2011.08.029)

Abstract

<p>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.</p> <p>Methods: The urothelium-lamina propria was isolated from guinea pig bladders, cut into strips (5 × 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 E₂ (PGE₂). Acetylcholine and PGE2 release was measured using a GeneBLAzer M3 CHO-K1-bla cell reporter assay and an enzyme immunoassay, respectively. The role of the muscarinic type 2 and 3 (M₂ and M₃, respectively) receptors and nitric oxide in mediating PGE₂ 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).</p> <p>Results: Acetylcholine release was detected in response to stretch and in the unstretched preparations exposed to PGE₂ 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 PGE₂ (half-maximal concentration 75 nM). The arecaidine stimulation of PGE₂ production was inhibited in a dose-dependent manner by the antagonist AFDX-116 (M₂ > M₃; half-maximal inhibition 110 nM) but not darifenacin (M₃ > > M₂). Finally, in the presence of the nitric oxide donor, NONOate, arecaidine-stimulated PGE₂ production was inhibited.</p> <p>Conclusion: These observations demonstrate that complex signal interactions occur within the urothelium involving acetylcholine, adenosine triphosphate, nitric oxide, and PGE₂. In addition, the data have demonstrated a role for muscarinic M₂ receptors and nitric oxide in the cholinergic regulation of PGE₂ production in the bladder wall.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nile, Dr Christopher
• Authors: Nile, C.J., and Gillespie, J.I.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Urology
• ISSN: 0090-4295
• Published Online: 07 November 2011