Characteristics of supersensitivity induced by the pretreatment with AF64A, an inhibitor of choline uptake at parasympathetic nerve endings, were examined in rat iris sphincter. In preparations Isolated and skinned by β-escin after the micro-injection of AF64A to eyes in vivo, the amplitude of maximum contraction in pCa 4.5 solution was increased by 180% of the control from the contralateral eyes. The Ca²⁺ sensitivity of the contractile system was slightly but significantly increased by AF64A injection; the half maximum contraction was obtained at pCa 5.87 and 6.05 in the control and AF64A-injected eyes, respectively. The increase in maximum contraction in AF64A-injected ones was neither affected by the addition of calmodulin, GTPγS nor H-7. The increase in Ca²⁺ sensitivity by AF64A injection was not affected by calmodulin, enhanced by GTPγS and abolished by H-7. AF64A injection increased the total protein content only by 30% of the control. The contents of contractile proteins per iris were quantified using Western blotting with monoclonal antibodies. The contents of actin and calponin were increased by AF64A, whereas those of myosin, calmodulin and caldesmon were not affected. The results indicate that AF64A-induced enhancement of the maximum contraction is not mainly due to the increase in the contents of major contractile proteins and that the increase in Ca²⁺ sensitivity could be due to the mechanism in which changes in protein kinase C and/or GTP binding protein activity are involved.

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We searched the effect of the muscular valve on the management of short bowel syndrome. The motility of the remnant intestine with a special muscular valve after 80% massive distal small bowel resection (MSBR) was evaluated in conscious dogs. The valve (muscular ring) was made by the autointestinal muscle layer holding vascular pedicle. Interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gauge force transducers 2-4 weeks after the surgery, and data of this group (Group I) were compared to the motility in dogs after MSBR without valve construction (Group II) and in controls (Control). Results; Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) in Group I occurred at longer intervals than in Control and almost similarly to those in Group II. MMCs arising from the duodenum were often interrupted before the jejunum above the valve and the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment including that from the duodenum to the proximal jejunum, and to the jejunum above the anastomosis. Transit time in MSBR group (I and II) from the duodenum to the terminal ileum was extremely shorter than in Control, but there were no differences between in Groups I and II. The duration of the postprandial period without duodenal MMCs in Group I was significantly prolonged than in Control, but was shorter than that in Group II. The muscular valve was frequently activated, and the jejunum covered with the valve was contracted frequently which synchronized with the valve activity. It seemed the valve worked as sphincter. However, intestinal obstruction was not occurred through the jejunum covered by the valve. In conclusion, changes in gut motility after MSBR with the valve construction compensate for the shortened intestine and maintain the bowel content earlier postoperatively in comparison with the MSBR alone, and also contribute to the adaptive increase in the remnant intestinal absorption.

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We studied the effects of Z-338, a newly synthesized carboxyamide derivative, on autonomic neuroeffector transmission in the guinea-pig stomach in relation to its gastro-intestinal prokinetic action, by use of tension recording and microelectrode methods. Z-338 (>10^-8M) dose-dependently enhanced the amplitude of twitch-like contractions and excitatory junction potentials (EJPs) evoked by single or repetitive electrical field stimulation (EFS) without affecting the non-adrenergic non-cholinergic (NANC) relaxation and inhibitory junction potentials (IJPs) in the circular muscle strips of the guinea-pig stomach. Similar to the action of Z-338, pirenzepine (>10^-8M), a muscarinic M₁-antagonist, enhanced the EJP amplitude, although AF-DX116 (M_2-) and 4-DAMP (M₃-antagonists) reduced the EJP amplitude, dose-dependently. The EC₅₀ of the Z-338 and pirenzepine concentration response curves on EJPS were 4.7×10^-8 M and 1.0×10^-8M, and Hill coefficients were 0.96 and 0.94 respectively. In addition, Z-338 slightly but significantly enhanced the amplitude of slow waves with or without initial spike. These results provide the first evidence that Z-338 exerts its gastrointestinal prokinetic action mainly through enhancing excitatory neuro-effector transmission with no effect on NANC inhibitory neuro-effector transmission in the guinea-pig stomach.

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