Sunagane N., T. Kobori, T. Uruno and K. Kubota. Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder. The spasmolytic action of bile salts on gallbladder smooth muscle could explain the alleged relief of biliary colic seen during bile acid therapy. The mechanisms of spasmolytic action of bile salts, ursodeoxycholate and deoxycholate were studied in the isolated gallbladder of guinea-pigs. The bile salts accelerated the ⁴⁵Ca-efflux from the gallbladder with synchronous relaxation and inhibited the cellular ⁴⁵Ca-uptake by the depolarized muscle preparation. Further, they sensitively inhibited CaCl₂-induced contraction of the depolarized muscle. The tissue cyclic AMP content of the gallbladder was significantly elevated by the bile salts. Dibutyryl cyclic AMP mimicked the effects of bile salts on the Ca-efflux and the muscle relaxation, but showed no effect on the cellular Ca-uptake. From these results, it is suggested that the bile salts produce the relaxant action through accelerating Ca-efflux, which is probably coupled with the elevation of the cellular cyclic AMP level, and through suppressing the Ca-influx across the cell membrane.

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Kamizaki, J., Shimizu, K., Nakajyo, S. and Urakawa, N. A change in inhibitory mechanism of Na⁺deficiency on high K⁺-induced contraction in rat uterus with the progress of pregnancy. Jpn. J. Smooth Muscle Res.
In the present paper, effects of high K⁺/Na⁺deficient solution on the rat uterus with the progress of the pregnancy were examined on the mechanical response and wet weight. The progress of pregnancy was divided in four stages, early stage (Day 4 and 5 of pregnancy), middle stage (Day 8-10), late stage (Day 14 and 15) and end stage (Day 21). In the early stage muscle, an isosmotically substituted high K⁺/Na⁺ deficient (iso-154K⁺) solution induced a large contraction followed by a decrease in tension level, though a hyperosmotic KCl addition induced a large sustained contraction. Similar results were shown in muscles of the middle and late stages, However, a maximum tension level and a subsequent inhibition by the iso-154K⁺ solution in the end stage muscle were smaller than those of other stages. On the other hand, iso-154K⁺solution remarkably increased the relative cellular water content in the early or middle stage muscle, but moderately in the late or end stage one. In the muscle of all stages, a hyperosmotic addition of sucrose reversed the inhibition of muscle tension and the cell swelling by the iso-154K⁺ solution. Moreover, a substitution of more impermeable anion (C₂H₅COO-) for Cl-in the iso-154K⁺solution decreased the inhibition of the contraction in the early stage muscle, but increased it in the end stage one. Thesubstitution for Cl-with more permeable anion (NO₃-or I-) produced a greater inhibition of contraction in all stage muscles. Moreover, a substitution of pyruvate or oxalacetate forglucose in iso-154K⁺solution did not affect the decreased tension in the early stage muscle, however, reversed the decreased tension in those after the middle stage. From these results, the decrease of the developed tension in the iso-154K⁺solution in the early stage muscle is probably due to cell swelling and those after the middle stages is probably caused by both the cell swelling and the inhibition of glucose utilization by Na⁺deficiency in the medium. The data suggest that the mechanism of the decrease in tension is probably transferred from cell swelling to inhibition of glucose utilization with the progress of pregnancy.

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The effect of AS-4370 given in single doses of 2.5, 5 and 10mg on gastric emptying was investigated using ^99mTc-DTPA in healthy volunteers in the placebocontrolled double-blind crossover design.
There was no difference in percent activity throughout the period of measurement between AS-4370 2.5mg and placebo. The percent activity decreased after administration of 5 and 10mg of AS-4370 in comparison with placebo: the decrease was found during the period from 10 to 18 minutes after start of recording at 5mg and from 8 to 18 minutes after start of recording at 10mg. These results demonstrated that AS-4370 at these dose levels apparently accelerated gastric emptying.
The analysis of the half emptying time by the crossover method showed that only the time effect was found at 2.5mg, whereas the half emptying time was obviously shortened at 5 and 10mg. There was no difference between 5mg and 10mg.
There was no finding that might warrant a caution in terms of safety.
In conclusion, AS-4370 did not affect gastric emptying at 2.5 mg but apparently accelerated gastric emptying at 5 and 10mg in healthy volunteers.

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LES pressure increase following diaphragmatic contraction as a pinch-cock action acts as one of the barrier mechanism for gastroesophageal reflux.
In achalasia patients, incomplete LES relaxation following wet swallow is one of the characteristic manometric findings, along with loss of peristalsis. On the other hand, it has been reported that swallowing effort or esophageal distention have no effect on the increase of LES pressure induced by diaphragmatic contraction, which condition is similar to achalasia.
Therefore, to evaluate that whether diaphragmatic contraction is involved in the cause of achalasia, we recorded diaphragmatic electromyography (DEMG) using bipolar electrodes in 12 achalasia patients and 4 normal subjects.
The phasic DEMG amplitude was 80-90, μV in normal subjects and achalasia patients. LES pressure and DEMG amplitude increasedduring both straight leg raising (SLR) and abdominal distention (AD), both of the maneuver induce diaphragmatic contraction, in normal subjects and achalasia patients similarly.
From the data obtained with this equipment, we conclude that diaphragmatic involvement is not likely as a pathogenesis of LES dysfunction in achalasia patients.

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The present study investigates the ureteral action potential and histological changes of pelvi-ureteral system after injection of the formalin into the obstracted ureters or the renal pelvis.
In the first experiment, formalin was injected into the obstracted ureters of 18 dogs for 30 minutes.
In the second, formalin was injected into the obstracted renal pelvis of 13 dogs for 30 minutes using ureteral balloon catheters, and then renal pelvis were released from obstraction and catheters were removed.
In these experiments, ureteral electromyogram were recorded and histological changes of pelvi-ureteral system were also observed microscopically.
Results
1. After injection of formalin into the ureters, ureteral action potential disappeared and had not restored.
Histologically, damage was observed in the ureteral smooth muscle as well as in the mucosa.
2. After injection of formalin into the renal pelvis, ureteral action potential disappeared in 46% of the ureters. In 54% of the ureters, action potential had not disappered, however discharge interval became irregular. Histological changes of the renal pelvis was not related to the presence or absence of ureteral action potential.
The results of the present study show that ureteral smooth muscle play part in the conduction of the ureteral excitation, and have an irregular autonomic discharge.

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