Effects of cisapride on the motility of the digestive tract in vivo in dogs and the guinea-pig intestine in vivo were studied.
1. Cisapride (0.05-2.0mg/kg, i.v.) produced an increase in amplitude of spontane-ous contractions and basal tone in the stomach, duodenum, jejunum and proximal and distal colon in dogs. In some animals, however, it induced an inhibition with decrease in amplitude and tone. It also induced an increase in amplitude of contractions in the gallbladder and the sphincter of Oddi in dogs. The tone of the gallbladder was elevated by the same dose of cisapride, but the tone of the sphincter of Oddi was decreased. The drug produced a reverse response in some animals. These excitatory responses to cisapride were abolished by atropine (0.2mg/kg, i.v.).
2. Motility of the guinea-pig isolated ileum and colon was enhanced with an increase in their amplitude of contractions and basal tone at low concentrations of cisapride (10^-9-10^-6M) but it was inhibited at higher concentrations (10^-5-10^-4M). Atropine abolished the excitatory response of the ileum to cisapride in all cases. It abolished the excitation of the colon in some preparations but reduced only in some degree in the other. The inhibitory effect of cisapride on isolated preparations was unaffected by tetrodotoxin.
3. From these results, it is concluded that cisapride enhances motility of the gatsrointestinal tract and biliary tract by acting on myenteric cholinergic neurons and inhibits it by acting on the smooth muscle itself.

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Immunobiochemical and immunohistochemical studies were performed to find out changes in neural and glial components of the intestine in congenital aganglionosis rats. Nervous system-specific enolase (NSE) was used as a marker of the neural component. S-100 protein was used as a marker of the glial component. NSE and S-100 protein were quantitated by highly sensitive immunoassay. And distribution of NSE and S-100 protein of the intestine was studied by immunohistochemical methods in fetal rats of various gestational age. The results of our studies were followed;
1) Significant decrease in NSE and S-100 protein was found in the aganglionic segment.
2) Although there was no decrease in NSE, significant decrease in S-100 protein was found in the ganglionic segment just proximal to the aganglionic narrow segment.
3) In the studies using rat embryos, NSE positive cells and S-100 protein positive cells were identified in the more caudal intestine with increasing gestational age. In addition, NSE positive cells appeared in the intestine few days earlier than S-100 protein positive cells did.
In conclusion, our studies disclosed that there was abnormality of the glial component as well as the neural component in the intestine of Hirschspung's disease.

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Yamada, T. and Obara, K. Changes in cyclic AMP and cyclic GMP levels in the contraction-relaxation cycle of isolated smooth muscle cells from guinea-pig taenia caeci. Japanese Journal of Smooth Muscle Research, 1985, 21 (1), 25-37.-The present study was undertaken to investigate the role of cyclic AMP and cyclic GMP in the regulation of the contraction-relaxation cycle in isolated smooth muscle cells from guinea pig taenia caeci. The contraction of isolated smooth muscle cells induced by both caffeine (4×10^-3M) and carbachol (10^-4M) consisted of an initial activation phase and a following spontaneous relaxation phase. Isoproterenol (10^-4M) inhibited the carbachol-induced contraction and raised intracellular cyclic AMP level of iso-lated smooth muscle cells. Both the inhibition of the carbachol-induced contraction and the rise in cyclic AMP level elicited by isoproterenol were blocked by propranolol (10^-4M). Caffeine increased intracellular cyclic AMP level significantly and con-tracted isolated smooth muscle cells. Caffeine and carbachol contracted isolated smooth muscle cells and increased intracellular cyclic GMP level. Cyclic GMP was significantly increased in spontaneous relaxation phase. The data suggest that β-adrenergic inhibitory effect on cholinergic excitation in the mammalian isolated smooth muscle cells is mediated by the change in intracellular cyclic AMP level and that cyclic GMP related to the relaxation in these single cells. Thus, it appears that caffeine-induced contraction might be due to the stimulation of Ca²⁺-induced Ca²⁺ release by cyclic AMP.

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Yamada, K. and Iizuka, M. Contractions of the stomach and duodenum induced by trimebutine in conscious fasted dogs. Japanese Journal of Smooth Muscle Research, 1985, 21 (1), 39-43-. Effect of trimebutine on the gastroduodenal motility was studied in conscious fasted dog with chronic implantation of electrodes and force transducers. During motor quiescence, trimebutine at 1.0-2.0 mg/kg i. v. produced action potentials and contractions similar to those developed during phase III (the period of intense action potential and contractile activity), which has been known to be physiologically important.
Metoclopramide (1.0-2.0 mg/kg i. v.) induced contractile activity different from that during phase III, and hyoscine-N-butylbromide (0.1 mg/kg i. v.) produced no action potentials and contractions.

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To study the motility functions after transection and anastomosis of the intestinal tract, the interdigestive action potential was induced experimentally and observed in the small intestines of conscious fasted dogs.
1. When the intestinal tract was transected, the frequency gradient of the basic electric rhythm was disturbed even in cases of subsequent anastomosis. Differences arose in the frequency as upper and lower part of anastomosis, and it did not return to normal.
2. The spike potential which appeared with the building up of the basic electric rhythm was propagated to the distal intestine in a normal course after transection of the intestinal tract according to observations centered on propagation of the IMEC.
3. The propapagation velocity of the IMEC gradually drops from the proximal jejunum toward the terminal ileum in the nonmanipulated intestine, while in the intestine undergoing transection and anastomosis, the velocity of propagation was reduced by half in the area of anastomosis, and tended to be even lower in cases of a double section and two anastomoses of the distal intestine. However, the total elapsed time in the small intestine was not extended by much.
4. A new electric complex appeared from the stump of the distal intestine when the intestine was subjected to transection, and a stimulation which is involved in the appearance of the spike potential was formed.

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Aschoori, F., Hidaka, H., Takai, A. & Tomita, T. Contraction of smooth muscle in Ca-free solution. Japanese Journal of Smooth Muscle Research, 1985, 21 (1), 57-69.-The tonic contractions which are extremely resistant to removal of the external Ca were investigated in the rat was deferens and myometrium. Both the noradrenaline response in the was deferens and the oxytocin response in the myometrium could be repeatedly produced without appreciable diminution in Ca-free solution for more than 24hrs. On the other hand, the tissue Ca content decreased exponentially after Ca-removal with a half time of 130-180min. When Ca was readmitted, no indication of the early transient contraction was observed in the subsequent response in Ca-free solution, but the response was reduced compared with the response before Ca readmission. Verapamil suppressed the response in the presence of Ca, while it had very weak inhibitory effect even at 10μM. Calmodulin antagonists of phenothi-azine derivatives had a strong inhibitory effect on Ca-induced contractions, whereas they had very weak effects on the receptor-mediated contraction in Ca-free solution. Another calmodulin antagonist, W-7 suppressed both Ca-induced contraction and the contractions independent of external Ca. HA-1004, a vasodilator which has a struc-ture similar to W-7, reduced the receptor-mediated contraction in Ca-free solution without much effect on Ca-induced contractions. These results may suggest that the receptor-mediated contractions resistant to Ca-removal are caused by some process without a contribution of the Ca-calmodulin system.

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The First Department of Physiology, Kawasaki Medical School, Kurashiki, Okayama (Director: Prof. M. Matsumura) The isolated guinea-pig gall-bladder showed the spontaneous changes in luminal pressure at the rate of7-12/min at38°C. These spontaneous contractions were increased in rates as the increase in luminal volume. On the other hand, they were reduced in rates and in amplitudes by lowering the temperatures. Decrease in [Ca²⁺] ₀ from 2.4 mM to 0.8 mM depressed or even abolished the spontaneous contractions, whereas increase in [Ca²⁺] ₀ from 2.4 mM to 7.2 mM produced slow pressure rise accompanied with small pressure fluctuations, suggesting that [Ca²⁺] _i was increased as the results of facilitation of Na-Ca exchange mechanism. The pressure-volume relation measured during the first inflation was steeper than that during the following deflation; namely, the gall-bladder showed plasticity. The visco-elastic property was investigated by recording the time course of the pressure change, stress relaxa-tion, following the sudden increase in volume. Thus, the tissue visco-elasticity was divided into threecomponents; the instantaneous elastic component and two visco- elastic components that had the time constants of 4-12 sec and of 5-10min.

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