title: Endogenous nitric oxide/cGMP signalling in the guinea pig bladder: evidence for distinct populations of sub-urothelial interstitial cells.
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 beta1 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.
authors.affiliation: The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University, NE2 4HH, Newcastle upon Tyne, England, UK. j.i.gillespie@ncl.ac.uk
authors.forename: J I
authors.initials: JI
authors.lastname: Gillespie
authors.forename: M
authors.initials: M
authors.lastname: Markerink-van Ittersum
authors.forename: J
authors.initials: J
authors.lastname: De Vente
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D015398:Signal Transduction; D014513:Ureter / Q000166:cytology* / Q000502:physiology; D001743:Urinary Bladder / Q000737:chemistry* / Q000166:cytology* / Q000502:physiology; D019459:Urothelium / Q000166:cytology*
chemical_list: D009569:Nitric Oxide; D006152:Cyclic GMP