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1 Enteric neuromuscular disorders and visceral pain center, Department of Internal Medicine, Physiology and Biophysics, The University of Texas Medical Branch, Galveston, TX, USA
* To whom correspondence should be addressed. E-mail: sksarna{at}utmb.edu.
We investigated the neuronal locus, the role PKC activation and utilization of extracellular Ca2+ and intracellular Ca2+ release in smooth muscle cells for the generation of giant migrating contractions (GMCs) and rhythmic phasic contractions (RPCs) in intact normal and inflamed canine ileum. Calcitonin gene-related peptide (CGRP), administered close intra-arterially stimulated GMCs at higher doses and RPCs at smaller doses. These effects were blocked by prior close intra-arterial infusions of CGRP8-37, atropine, hexamethonium, and tetrodotoxin (TTX), but not by tachykinin, serotonin and histaminergic receptor subtype antagonists. Both types of contractions were blocked by verapamil in normal and inflamed ileums. Dantrolene and ruthenium red blocked only the RPCs in normal ileum, but both GMCs and RPCs in the inflamed ileum. PKC inhibition by chelerythrine blocked GMCs only in inflamed ileum but RPCs in both normal and inflamed ileums. The inhibition of phospholipase C by neomycin blocked both RPCs and GMCs in normal and inflamed ileums. In conclusion, acetylcholine is the common neurotransmitter for the stimulation of both GMCs and RPCs, but the signaling cascades for their stimulation are partially divergent, and they differ also in the normal and inflamed states.
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