Endogenous nitric oxide/cGMP signalling in the guinea pig bladder: evidence for distinct populations of sub-urothelial interstitial cells |
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Authors: | JI Gillespie M Markerink-van Ittersum J De Vente |
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Institution: | (1) The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University, NE2 4HH Newcastle upon Tyne, England, UK;(2) European Graduate School of Neuroscience (EURON), Department of Psychiatry and Neuropsychology, Maastricht University, POB 616, 6200D Maastricht, The Netherlands |
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Abstract: | We have examined structures that may operate by using nitric oxide (NO)/soluble guanylyl cyclase (sGC) signalling in the lamina propria of the guinea pig bladder. Cells on the luminal surface of the urothelium and sub-urothelial interstitial cells (SU-ICs) responded to NO with a rise in cGMP. The distribution of these different cells varied between the base, lateral wall and dome. In the base, two regions were identified: areas with sparse surface urothelial cells and areas with a complete covering. A layer of cGMP-positive (cGMP+) cells (up to 10 cells deep) was found in the base. cGMP+/SU-ICs were also observed in the lateral wall. However, here, the cGMP+ cells were confined to a layer of only 1–2 cells immediately below the basal urothelial layer (basal cGMP+/SU-ICs). Below these cGMP+/SU-ICs lay cells that had a similar structure but that showed little cGMP accumulation (deep cGMP–/SU-ICs). Both basal and deep SU-ICs expressed the β1 subunit of sGC and the cGMP-dependent protein kinase I (cGKI), suggesting that the deep SU-ICs can sense NO and signal via cGMP. By using BAY 41-2272, a sensor of endogenous NO production, NO-dependent cGMP synthesis was observed primarily in the basal SU-ICs. A third population of cGKI+/cGMP− cells was seen to lie immediately below the basal urothelial layer. These cells (“necklace” cells) were less numerous than SU-ICs and extended linking processes suggesting a network. The specific functions of these structures are not known but they may contribute to the emerging multiple roles of the urothelium associated with the generation of bladder sensation. |
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Keywords: | cGMP Bladder Urothelium Nitric oxide Interstitial cells Guinea pig |
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