Ovarian Cancer G protein-coupled receptor-1 signaling bias dictates anti-contractile effect of benzodiazepines on airway smooth muscle.
Publication/Presentation Date
5-13-2025
Abstract
BACKGROUND: We recently reported that the ovarian cancer G protein-coupled receptor-1 (OGR1) can be pharmacologically biased with specific benzodiazepines to couple with distinct heterotrimeric G proteins in human airway smooth muscle (ASM) cells. Lorazepam stimulated both G
METHODS: Models of histamine (His) -stimulated contraction included imaging of ex vivo human precision cut lung slices (hPCLS) and Magnetic Twisting Cytometry (MTC) analysis of human ASM cell stiffness. To explore mechanisms of regulation, we examined effects on myosin light chain (pMLC) phosphorylation and PKA activity in primary human ASM cultures, as well as actin cytoskeleton integrity as defined by changes in the ratio of F to G actin assessed by immunofluorescence.
RESULTS: In a dose-dependent manner, sulazepam relaxed His-contracted hPCLS and reduced baseline cell stiffness. Lorazepam did not relax His-contracted hPCLS, and only at a maximal dose (100 μM) did lorazepam relax baseline cell stiffness. The G
CONCLUSIONS: The G
Volume
26
Issue
1
First Page
183
Last Page
183
ISSN
1465-993X
Published In/Presented At
Villalba, D. R., Jannu, A. K., Javed, E., Dandekar, I., Wang, R., Deshpande, D. A., An, S. S., Panettieri, R. A., Jr, Tang, D. D., Penn, R. B., & Nayak, A. P. (2025). Ovarian Cancer G protein-coupled receptor-1 signaling bias dictates anti-contractile effect of benzodiazepines on airway smooth muscle. Respiratory research, 26(1), 183. https://doi.org/10.1186/s12931-025-03268-9
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
40361189
Department(s)
Administration and Leadership
Document Type
Article