Carbachol stimulation of the muscarinic acetylcholine m1 receptor (m1R), stably expressed in Rat 1a fibroblasts, resulted in a calcium-dependent activation of c-Jun kinase (JNK). Stimulation of the muscarinic acetylcholine m2 receptor (m2R), stably expressed in Rat 1a fibroblasts, resulted in a G1-mediated activation of JNK that was weak relative to that observed with the m1R. Chelation of calcium inhibited the m2R-mediated activation of JNK but not the robust m2R stimulation of mitogen-activated protein kinase (MAPK) activity. These findings demonstrate a role for the second messenger, calcium, in the differential regulation of the activity of JNK and MAPK in Rat 1a cells.

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