Urothelium muscarinic activation phosphorylates CBS(Ser227) via cGMP/PKG pathway causing human bladder relaxation through H2S production.
作者： Roberta d’Emmanuele di Villa Bianca , Emma Mitidieri , Ferdinando Fusco , Annapina Russo , Valentina Pagliara
DOI: 10.1038/SREP31491
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摘要: The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances production in turn cGMP or cells. This effect is reversed cysthationine-β-synthase (CBS) inhibition. blockade M1 M3 receptors reverses increase urothelium. In cells, receptor significantly reduces carbachol-induced production. functional studies, removal from strips leads to an contraction that mimicked CBS Instead, CSE does affect contraction. driven CBS-cGMP/PKG-dependent phosphorylation at Ser(227) carbachol stimulation. finding presence this crosstalk between cGMP/PKG pathway M1/M3 further implies a key role for physiopathology. Thus, modulation can represent feasible therapeutic target develop drugs disorders.
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