M1, M3 and M5 muscarinic receptors stimulate mitogen-activated protein kinase.

Abstract

We report here that the M1, M3 and M5 muscarinic acetylcholine receptor subtypes that have been shown to couple to phosphoinositide hydrolysis also activate the mitogen-activated protein kinase (MAPK). Pharmacological characterization as well as mechanistic details of the activation pathway are presented. Carbachol-induced MAPK activation was time- and concentration-dependent at all subtypes. Pharmacological characterization of the MAPK response revealed that McN-A-343 was a partial agonist at the M1 and M3 subtypes, and that pilocarpine was a partial agonist at the M3 and M5 receptors. Carbachol-mediated MAPK activation at these receptor subtypes was pertussis toxin and wortmannin insensitive. By contrast, both agents significantly inhibited carbachol-induced MAPK activation by the M2 muscarinic receptor subtype. Furthermore, two independent single point mutations in the M1 receptor attenuated carbachol-induced activation of MAPK. Activation of MAPK at the M1, M3 and M5 muscarinic receptor subtypes was not dependent on intracellular or extracellular Ca2+, but was partially dependent upon protein kinase C. These data suggest that activation of MAPK by M1, M3 and M5 muscarinic receptors involves protein kinase C-dependent and independent pathways.

Cite this paper

@article{Wotta1998M1MA, title={M1, M3 and M5 muscarinic receptors stimulate mitogen-activated protein kinase.}, author={D R Wotta and Elizabeth V. Wattenberg and R B Langason and EE El-Fakahany}, journal={Pharmacology}, year={1998}, volume={56 4}, pages={175-86} }