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NEUROREGULATION AND MOTILITY

PKC- translocation in enteric neurons and interstitial cells of Cajal in response to muscarinic stimulation

¹Department of Physiology and Cell Biology and ²Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada 89557

Submitted 26 September 2002 ; accepted in final form 15 April 2003

Interstitial cells of Cajal in the deep muscular plexus (ICC-DMP) of the small intestine express excitatory neurotransmitter receptors. We tested whether ICC-DMP are functionally innervated by cholinergic neurons in the murine intestine. Muscles were stimulated by intrinsic nerves and ACh and processed for immunohistochemistry to determine these effects on PKC- activation. Under control conditions, PKC--like immunoreactivy (PKC--LI) was only observed in myenteric neurons within the tunica muscularis. Electrical field stimulation or ACh caused translocation of neural PKC--LI from the cytosol to a peripheral compartment. After stimulation, PKC--LI was found in spindle-shaped cells in the DMP. These cells were identified as ICC-DMP by Kit-LI and vimentin-LI. PKC--LI in ICC-DMP and translocation of PKC-LI in neurons were blocked by tetrodotoxin or atropine, suggesting that these responses were due to activation of muscarinic receptors. Western blots also confirmed translocation of PKC--LI. In conclusion, PKC- translocation is linked to muscarinic receptor activation in ICC-DMP and a subpopulation of myenteric neurons. These studies demonstrate that ICC-DMP are functionally innervated by excitatory motoneurons.

muscarinic receptor; enteric nervous system; gastrointestinal motility

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