Fujii, K., Okajima, M., Kawahori, K., Murakami, Y. and Shimatani, T. Effect of α₂-adrenergic receptor antagonist (Midaglizole) on gastrointestinal motility in conscious dogs. Jpn. J. Smooth Muscle Res., 1989, 25 (4), 000-000, 1989 To clarify the physiological role of the mechanism that adrenergic nerve inhibits Ach release from intramural cholinergic nerve endings, the influence of Midaglizole, α₂-adrenergic receptor antagonist, to postpran-dial gastrointestinal motilities in conscious dogs was investigated.
Postprandial motilities of gastric antrum, duodenum, ileum, and colon were significantly enhanced by Midaglizole (3.0-5.0 mg/kg body weight, i.v, ). These excitatory responses were abolished by atropine (0.05-0.1 mg/kg body weight, i.v.). On the other hand, in most cases (29 cases out of 32), when Midaglizole was administered during quiesent phase of IMC, no change occurred in gastrointestinal motility. However, after subliminal dose of pentagastrin or cisapride, which stimulated Ach release from intramural cholinergic neuron without development of motility, was administered, Midaglizole induced phasic, postpran-dial motility-like contraction in gastrointestinal tract. Even in the fasted state, when Midaglizole was administered intragastrically, irregular contractions with high amplitude occurred in every regions from gastric antrum to colon. And these excitatory responses were abolished by atropine. Similar reaction was observed also in truncal vagotomized dogs.
These results suggest that it is the physiological mechanism that adrenergic nerve presynaptically inhibits Ach release from intramural cholinergic neuron, which is the main mechanism of development of postprandial motility, acting on α₂-adrenergic receptor, and has tonic control of postprandial motility.

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The colonic motilities during defecation were studied by means of extraluminal strain gauge force transducers in six conscious dogs. A set of eight transducers was implanted in each dog: one was on the terminal ileum and the remaining sev0en were on the whole length of the colon equidistantly.
As Karaus & Sarna had already described in 1987, giant migrating contractions (GMC) that were initiated in the proximal colon and rapidly migrated caudad before defecation were reconfirmed also in this study to be motor equivalent of mass movements. Several new findings in addition were obtained.
At spontaneous defecation, a reflex relaxation was always observed at the distal end of the colon. This colonic outlet relaxation (COR) usually occurred synchronously with the initiation of GMC at the proximal colon and lasted until GMC had arrived at the distal end. Evacuation of feces occurred during this COR. COR was not observed at defecation induced by neostigmine or prostaglandin F₂α.
After bilateral pelvic nerve section, both GMC and COR were completely abolished. Instead, group of low amplitude caudad migrating contractions occurred at the proximal or middle colon and were followed by frequent evacuation of small amount of loose stools. COR was not observed at this type of defecation.
It is suggested from this study that not only GMC but also COR are the essential motor correlates of spontaneous defecation. Both GMC and COR are under control of pelvic nerves.

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The purpose of this study is to examine the role of peptidergic nerves (VIP, Substance P, Neurotensin) in Hirschsprung's disease (aganglionosis) and hypoganglionosis in relation to the normoganlionic state of the colon using a mechanographic technique in vitro.
The following results were obtained.
1) Normoganglionic muscle strips demonstrated the presence of intact non-adrenergic inhibitory nerve. The activities of such nerves, however, were reduced in hypoganglionic muscle strips, and were absent in aganglionic muscle strips.
2) Peptidergic nerve activities by VIP, substance P, and Neurotensin were present in normoganglionic muscle strips, while they were reduced in hypoganglionic muscle strips, and absent in aganglionic muscle strips.
3) VIP may act as a neurotransmitter-neuromodulator of non-adrenergic inhibitory nerve, while SP and Neurotensin may act as that of non-cholinergic excitatory nerve with some direct effect on the intestinal muscle.

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Anti-cholinesterase activity of dopamine D₂ receptor antagonist, domperidone was studied by means of chronically implanted force transducers in the gastrointestinal (GI) tract in five conscious dogs. Cisapride was used as a drug to stimulate endogenous release of acetylcholine. In the digestive state, cisapride (0.25 mg/kg) stimulated 18.6±5.6% increase in the motor index of the gastric antrum alone, however, combined administration with domperidone (1.0 mg/kg-hr) significantly enhanced the motor index in the gastric antrum and duodenum. In the gastric antrum, the increase was 68.1±7.2%. During the interdigestive state, ciaspride did not always induce the interdigestive migrating contrac-tions (IMC)-like contractions in the GI tract, but the background infusion of domperidone significantly increased the incidence of the occurrence of IMC-like contractions by cisapride. In in vitro study, weak but significant anti-cholinestrase activity was found in domperidone, the activity being about 1/1, 000 of that of neostigmine. In dog experiment, similar enhance-ment of motor stimulating activity of cisapride was observed when neostigmine was given at 1.0 μg/kg-hr. In conclusion, domperidone has anti-cholinesterase activity and acts to enhance motor stimulating activity of cisapride through inhibition of cholinesterase activity in the upper digestive tract.

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