The objective of this project is to enhance the understanding of the role of the neuron-associated gastrointestinal peptides in the control of colonic smooth muscle activity. Myoelectrical activity will be measured in isolated smooth muscle from the transverse colon of the cat. Myoelectrical activity will be measured from colonic tissue with an intact myenteric plexus by glass pore electrodes. Myoelectrical dnd contractile activity will be measured from pure circular or longitudinal smooth muscle using a sucrose gap and a force displacement transducer. The effect of the gastrointestinal peptides, vasoactive intestinal peptide, substance P, or the enkephalins will be determined on innervated and denervated colonic smooth muscle. Antagonists of the autonomic nervous system will be used to determine if the gastrointestinal peptides act directly on smooth muscle or through neural receptors. The CCK receptor antagonist, dibutyryl cGMP will clarify the action of the octapeptide of cholecystokinin on colonic smooth muscle. A double sucrose gap will be used to estimate the membrane conductance and ionic current flows during the administration of the gastrointestinal peptides. The release of the peptides from the myenteric plexus or the smooth muscle after electrical field stimulation will be measured by radioimmunoassay. Changes in the tissue levels of these peptides or an alteration in the pattern of their presence will be performed by immunohistopathology. Surgical specimens of human colonic smooth muscle from patients with diverticular disease, ulcerative colitis, or granulomatous colitis will be studied with the double sucrose gap. Changes in membrane conductance, or electromechanical coupling will be measured in these tissues from diseased patients.
