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In response to G protein-coupled receptor (GPCR) stimulation, the urinary bladder detrusor muscle has shown a 70% dependence on extracellular calcium, whereas the urothelium and lamina propria (U&amp;LP) has a 20%\u201350% dependence. However, as this only accounts for partial contractile activity, the contribution of intracellular calcium and calcium sensitization pathways remains unclear. This study assessed the role of intracellular signaling pathways on GPCR-mediated urinary bladder U&amp;LP contraction. Porcine U&amp;LP responses to activation of the G<jats:sub>q\/11<\/jats:sub>-coupled muscarinic, histamine, 5-hydroxytryptamine (serotonin), neurokinin, prostaglandin, and angiotensin II receptors were assessed with three selective inhibitors of store-released intracellular calcium, 2-aminoethyl diphenylborinate (2-APB), cyclopiazonic acid (CPA), and ruthenium red, and three Rho kinase inhibitors, fasudil, Y-27632, and GSK269962. There was no discernible impact on receptor agonist-induced contractions of the U&amp;LP after blocking intracellular calcium pathways, suggesting that this tissue is more sensitive to alterations in the availability of extracellular calcium. However, an alternative mechanism of action for GPCR-mediated contraction was identified to be the activation of Rho kinase, such as when Y-27632 significantly reduced the GPCR-mediated contractile activity of the U&amp;LP by approximately 50% ( P &lt; 0.05, n = 8). This suggests that contractile responses of the bladder U&amp;LP do not involve a significant release of calcium from intracellular stores, but that G<jats:sub>q\/11<\/jats:sub>-coupled receptor activation causes calcium sensitization via Rho kinase. This study highlights a key role for Rho kinase in the urinary bladder, which may provide a novel target in the future pharmaceutical management of bladder contractile disorders. <\/jats:p>","DOI":"10.1152\/ajpcell.00441.2022","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T20:16:47Z","timestamp":1674505007000},"page":"C787-C797","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["The role of intracellular calcium and Rho kinase pathways in G protein-coupled receptor-mediated contractions of urinary bladder urothelium and lamina propria"],"prefix":"10.1152","volume":"324","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4217-0214","authenticated-orcid":false,"given":"Charlotte","family":"Phelps","sequence":"first","affiliation":[{"name":"Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, 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