Neuronal locus and cellular signaling for stimulation of ileal giant migrating and phasic contractions

We investigated the neuronal locus, the role of 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 CGRP_8-37, atropine, hexamethonium, and 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 blocked both GMCs and RPCs in the inflamed ileum. PKC inhibition by chelerythrine blocked GMCs only in inflamed ileum but blocked 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.