Abstract
The purpose of this study was to determine whether Src tyrosine kinases are one of the signaling intermediaries linking M(2) receptor stimulation to extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) in cultures of canine colonic smooth muscle cells (CSMC). RT-PCR studies demonstrate expression of multiple Src tyrosine kinases, including Src, Fyn, and Yes, in CSMC. Muscarinic stimulation of CSMC with 10 microM ACh results in a twofold increase in Src activity within 10 min but does not increase the activity of Fyn. Treatment with the M(2) antagonist AF-DX 116 (10 microM) blocks ACh-stimulated Src activation in primary CSMC cultures that express both M(2) and M(3) receptors and in first-passage CSMC cultures that express predominantly M(2) receptors. Alkylation of M(3) receptors with 100 nM N,N-dimethyl-4-piperidinyl diphenylacetate mustard has no effect on Src activity. Treatment with the pyrazolopyrimidine Src inhibitor PP1 (10 microM) or AF-DX 116 (10 microM) blocks ACh-stimulated ERK phosphorylation. Together these results indicate that M(2) receptors are coupled to Src tyrosine kinase and subsequent activation of ERK in cultured CSMC.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: American journal of physiology. Gastrointestinal and liver physiology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.