Tachykinins and in vivo gut motility

The gut smooth muscle in the intact conscious state exhibits three distinct types of contractions: rhythmic phasic contractions, tone, and ultrapropulsive contractions. The motility functions of these contractions differ markedly. The phasic contractions mix and propel the ingested food in an orderly fashion so that the nutrients can be absorbed. The ultrapropulsive contractions are of two types, giant migrating contractions (GMCs) and retrograde giant contractions (RGCs). GMC's produce mass movements in the caudal direction and RGC's in the oral direction. GMCs are associated with the symptoms of diarrhea, abdominal cramping, tenesmus, and urgency of defecation. The RGCs regurgitate the contents of the upper small intestine into the stomach in preparation of their expulsion by the somatomotor response. Tachykinins and their receptors are strategically located on the enteric neurons and smooth muscle cells to regulate the above contractions. Recent findings show that NK-1 receptors located on colonic circular smooth muscle cells may mediate colonic GMC's, whereas NK-3 receptors located on presynaptic neurons may mediate the small intestinal GMC's. The molecular and cellular mechanisms of stimulation of RGC's are not known. NK-1 receptor antagonists have shown potential therapeutic effects on vomiting induced by a variety of stimuli in experimental animals.