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West Ashley Library
9 a.m. - 5 p.m.
Phone: (843) 766-6635
Wando Mount Pleasant Library
9 a.m. - 5 p.m.
Phone: (843) 805-6888
Village Library
9 a.m. - 1 p.m.
Phone: (843) 884-9741
St. Paul's/Hollywood Library
9 a.m. - 5 p.m.
Phone: (843) 889-3300
Otranto Road Library
9 a.m. - 5 p.m.
Phone: (843) 572-4094
Mt. Pleasant Library
9 a.m. – 5 p.m.
Phone: (843) 849-6161
McClellanville Library
9 a.m. – 1 p.m.
Phone: (843) 887-3699
Keith Summey North Charleston Library
9 a.m. - 5 p.m.
Phone: (843) 744-2489
John's Island Library
9 a.m. - 5 p.m.
Phone: (843) 559-1945
Hurd/St. Andrews Library
9 a.m. - 5 p.m.
Phone: (843) 766-2546
Folly Beach Library
9 a.m. - 2 p.m.
*open the 2nd and 4th Saturday
*open the 2nd and 4th Saturday
Phone: (843) 588-2001
Edisto Island Library
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Phone: (843) 869-2355
Dorchester Road Library
9 a.m. - 5 p.m.
Phone: (843) 552-6466
John L. Dart Library
9 a.m. - 5 p.m.
Phone: (843) 722-7550
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9 a.m. - 5 p.m.
Phone: (843) 795-6679
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9 a.m. - 5 p.m.
Phone: (843) 805-6930
Bees Ferry West Ashley Library
9 a.m. - 5 p.m.
Phone: (843) 805-6892
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Closed for renovations
Phone: (843) 883-3914
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Phone: (843) 805-6909
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Intracellular signaling pathways of muscarinic acetylcholine receptor-mediated detrusor muscle contractions.
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- Author(s): Balla, Helga; Borsodi, Kinga; Őrsy, Petra; Horváth, Béla; Molnár, Péter József; Lénárt, Ádám; Kosztelnik, Mónika; Ruisanchez, Éva; Wess, Jürgen; Offermanns, Stefan; Nyirády, Péter; Benyó, Zoltán
- Source:
American Journal of Physiology: Renal Physiology; Nov2023, Vol. 325 Issue 5, pF618-F628, 11p - Source:
- Additional Information
- Abstract: Acetylcholine plays an essential role in the regulation of detrusor muscle contractions, and antimuscarinics are widely used in the management of overactive bladder syndrome. However, several adverse effects limit their application and patients' compliance. Thus, this study aimed to further analyze the signal transduction of M
2 and M3 receptors in the murine urinary bladder to eventually find more specific therapeutic targets. Experiments were performed on adult male wild-type, M2 , M3 , M2 /M3 , or Gαq/11 knockout (KO), and pertussis toxin (PTX)-treated mice. Contraction force and RhoA activity were measured in the urinary bladder smooth muscle (UBSM). Our results indicate that carbamoylcholine (CCh)-induced contractions were associated with increased activity of RhoA and were reduced in the presence of the Rho-associated kinase (ROCK) inhibitor Y-27632 in UBSM. CCh-evoked contractile responses and RhoA activation were markedly reduced in detrusor strips lacking either M2 or M3 receptors and abolished in M2 /M3 KO mice. Inhibition of Gai-coupled signaling by PTX treatment shifted the concentration-response curve of CCh to the right and diminished RhoA activation. CCh-induced contractile responses were markedly decreased in Gαq/11 KO mice; however, RhoA activation was unaffected. In conclusion, cholinergic detrusor contraction and RhoA activation are mediated by both M2 and M3 receptors. Furthermore, whereas both Gai and Gαq/11 proteins mediate UBSM contraction, the activation at the RhoA-ROCK pathway appears to be linked specifically to Gαi . These findings may aid the identification of more specific therapeutic targets for bladder dysfunctions. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of American Journal of Physiology: Renal Physiology is the property of American Physiological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
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