Contribution of Postjunctional M2 Muscarinic Receptors to Cholinergic Nerve-Mediated Contractions of Murine Airway Smooth Muscle

Tuleen Alkawadri, Lorcan P McGarvey, N D Mullins, Mark A Hollywood, Keith D Thornbury, Gerard P Sergeant

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
28 Downloads (Pure)

Abstract

Abstract bronchoconstrictor effects of acetylcholine. In this study, we describe a novel and profound M2R-mediated hypersensitization of M3R-dependent contractions of ASM at low stimulus frequencies.. Contractions induced by 2Hz EFS were augmented by > 2.5-fold when the stimulus interval was reduced from 100 to 10 s. This effect was reversed by the M2R antagonists, methoctramine, and AFDX116, and was absent in M2R null mice. The M3R antagonist 4-DAMP abolished the entire response in both WT and M2R KO mice. The M2R-mediated potentiation of EFS-induced contractions was not observed when the stimulus frequency was increased to 20 Hz. A subthreshold concentration of carbachol enhanced the amplitude of EFS-evoked contractions in WT, but not M2R null mice. These data highlight a significant M2R-mediated potentiation of M3R-dependent contractions of ASM at low frequency stimulation that could be relevant in diseases such as asthma and COPD.
Original languageEnglish
Article numberzqab053
Number of pages11
JournalFunction
Volume3
Issue number1
Early online date20 Oct 2021
DOIs
Publication statusPublished - 16 Dec 2021

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