Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions.

We examined the action of key neurotransmitters - purinergic and muscarinic agonists on ATP release and its paracrine effect. Guinea-pig and human urothelial mucosae were mounted in a perfusion trough; superfusate ATP was measured using luciferin-luciferase assay and tissue contractions were recorded with a tension transducer. Intracellular calcium was measured in isolated urothelial cells with Fura-2. P2Y agonist UTP but not P2X agonist α,β-methylene-ATP, generated ATP release. Muscarinic agonist carbachol and M2-preferential agonist oxotremorine also generated ATP release, antagonized by M2-specific agent methoctramine. Agonist-evoked ATP release was accompanied by mucosal contractions. Urothelial ATP release was differentially mediated by intracellular calcium release, c-AMP, exocytosis or connexins. Urothelium-attached smooth muscle exhibited spontaneous contractions that were augmented by sub-threshold concentrations of carbachol which had little direct effect on smooth muscle. This activity was attenuated by desensitizing P2X receptors on the smooth muscle. Urothelial ATP release was increased in aging bladders. Purinergic and muscarinic agents produced similar effects in human urothelial tissue. This is the first demonstration of specific modulation of urothelial ATP release in native tissue by purinergic and muscarinic neurotransmitters via distinct mechanisms. Released ATP produces paracrine effects on underlying tissues. This process is altered during aging and ha...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research