Ovarian Cancer G Protein-Coupled Receptor-1 Signaling Bias Dictates Anti-contractile Effect of Benzodiazepines on Airway Smooth Muscle

Authors

Dominic R. Villalba, Thomas Jefferson UniversityFollow
Arun K. Jannu, Thomas Jefferson UniversityFollow
Elham Javed, Thomas Jefferson UniversityFollow
Isha Dandekar
Ruping Wang
Deepak A. Deshpande, Thomas Jefferson UniversityFollow
Steven S. An
Reynold A. Panettieri
Dale D. Tang
Raymond B. Penn, Thomas Jefferson UniversityFollow
Ajay P. Nayak, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

5-13-2025

Comments

This article is the author's final published version in Respiratory Research, Volume 26, Issue 1, 2025, Article number 183.

The published version is available at https://doi.org/10.1186/s12931-025-03268-9.

Copyright © The Author(s) 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

Recommended Citation

Villalba, Dominic R.; Jannu, Arun K.; Javed, Elham; Dandekar, Isha; Wang, Ruping; Deshpande, Deepak A.; An, Steven S.; Panettieri, Reynold A.; Tang, Dale D.; Penn, Raymond B.; and Nayak, Ajay P., "Ovarian Cancer G Protein-Coupled Receptor-1 Signaling Bias Dictates Anti-contractile Effect of Benzodiazepines on Airway Smooth Muscle" (2025). Center for Translational Medicine Faculty Papers. Paper 131.
https://jdc.jefferson.edu/transmedfp/131

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

40361189

Language

English