J.Jpn. Surg. Soc.. 62(3): 340-361, 1961

---

STUDIES ON ACETYLCHOLINE DURING ILEUS

In the investigations on the fluctuation of acetylcholine in the central nervous tissues of the brain and spinal cord, Matsukura, Tsubata and others have demonstrated a market reductions of this substance in shch tissues during ileus. However, the problem as to the mechanism of such a change during ileus still remains unsolved. The author has attempted to elucidate this mechanism, using dogs as experimental animals, by determining the levels of cholinesterase, an enzyme responsible for decomposing acetylcholine and that of choline acetylase which is an emzyne involved in the synthesis. The results may be summarized as follows :
1. (1) The activity values of cholinesterase in the central nervous tissne of the brain under normal conditions were; in the thalamus the maximum was 395.2 CO₂ mm³/0.1 g/30 min, the minimum 281.2 CO₂ mm³/0.1g/30 min, giving an average of 352.6 CO₂ mm³/0.1 g/30 min, which proved to be the highest of all tissues studied. The intermediate activity values were obtained from the cerebellum, the maximum being 340.4 CO₂ mm³/0.1 g/30 min, the minimum 262.4 CO₂ mm³/0.1 g/30 min with an average of 309.3 CO₂ mm¹/0.1 g/30 min, followed by the medulla oblougata with the maximum of 275.2 CO₂ mm²/0.1 g/30 min, the minimum of 218.8 CO₂ mm³/0.1 g/30 min, giving an average of 243.9 CO₂ mm³/0.1 g/30 min. The cerebrum itself yielded the lowest value with the maximum of only 58.8 CO₂ mm³/0.1 g/30 min, the minimum of 36.4 CO₂ mm³/0.1 g/30 min, and an average of 53.3 CO₂ mm³/0.1 g/30 min.
(2) At the time of ileus these activity values of cholinesterase in the central nervous tissued of the brain are found to decrease gradually in any portion during its course. This decrease occurs rapidly during shock end to an extreme degree at the time of death when the thalamus gives -85.1%, the cerebellum -81.8%, the medulla oblongata -44.2%, and the brain -43.4% in the reduction rate.
(3) Under normal conditions the activity values of cholinesterase in the central nervons tissues of the spinal cord are as follows; in the lumber cord the valus were the highest, the maximum being 91.9 CO₂ mm³/0.1g/30 min. the minimum 49.2 CO₂ mm³/0.1 g/30 min, with an average of 66.05 CO₂ mm³/0.1g/30. min. This is followed by cervical cord which showed the maximum of 52.1 CO₂ mm¹/0.1 g/30. min, the minimum of 20.1 CO₂ mm³/0.1 g/30 min, giving an average of 30.35 CO₂ mm³/0.1 g/30 min. Then the lowest values were those of thoracic cord, the maximum being 42.5 CO₂ mm³/0.1 g/30 min, the minimum 11.0 CO₂ mm³/0.1 g/30 min, with an average of 25.8 CO₂ mm³/0.1 g/30 min.
(4) There is a tendency for the activity values of cholinesterase to imerease temporarily in the course of ileus at any portion of the central nervous tissue of the spinal cord. However, the values gradually decrease thereafter and at the time of death the lumbar cord shows -39.5%, the cervical cord -41.6% and the thoracic cord -37.7% of the reduction rate.
These results indicate that in the course of ileus the activity values of cholinesterase in the central narvous tissues of the spinal cord are remarkably reduced at all portions.
2. (1) The activity values of choline acetylase in the central nervous tissues of the brain under normal conditions are as follows : the thalamus shows the highest values, the naximum being 166.9 γ/g/h, the minimum 95.1 γ/g/h, with an average of 139.3 γ/g/h. This is followed by the medulla oblongata with the maximum of 104.2 γ/g/o, the minimum 41.7 γ/g/h, giving an average of 80.8 γ/g/h. The cerebrum gives the maximum of 65.6 γ/g/h, the minimum 33.5 γ/g/h, with an average of 54.2 γ/g/h. These values of choline acetylase activity show a tendency quite in agreement with that of acetylcholine content of the central nervous tissues of the brain under normal condition.
(2) At the time of ileus these activity values of choline acetylase in the central nervous tissues of the1 brain show very little changes.
(3) Under normal conditions the activity values of choline acetylase in the central nervous tissues of the spinal cord were as follows ; the highest velues were obtaimed from the lumber cord where the maximum was 232.6 γ/g/h, the miuimum 196.2 γ/g/h, and an average of 221.4 γ/g/h, followed by the cervical cord with the maximum of 150.8 γ/g/h, the minimum of 119.2 γ/g/h, and an average of 134.1 γ/g/h. The lowest values were found in the thoracic cord with the maximum of 95.4 γ/g/h, the minimum of 7.25 γ/g/h, giving an average of 82.6 γ/g/h. These findings demonstrate that the changes in the activity values of choline acetylase parallel those of acetylcholine contents in the central nervous tissues of the spinal cord.
(4) At the time of ileus the activity values of cholin acetylase in the central nervous tissues of the spinal cord change little at any portion. Likewise, there are little changes in the activity level of choline acetylase at any portion of the central nervous tissues of the brain.
Generalizing the findings of investigations on choline esterase and choline acetylase, it can be stated that the activity values of cholinesterase in the central nervous tissues of the brain and spinal cord during ileus are greatly reduced in accordance with its course, but very little changes are noted in the activity leval of choline acetylase.
From these results the author has come to concluds that the decreased values of acetylcholine in the central narvous tissues of the brain and spinal cord at the time of ileus depend neither on the fluctuations in its decomposing enzyme, cholinesterase, nor on the changes in its synthesizing ferment, choline acetylase.
Such being the case, the author in an effort to ascertain the mechamism of acetylcholine reduction investigated the quantitative changes of acetylcholine content in the blood of both carotid artery and jugular vein supplying the central nervous tissues of the brain during ileus, in addition to the observations on the fluctuations of acetylcholine and cholinesterase in the cerebrospinal fluid. The results of these observations may be summarized as follows :
I. (1) Under normal conditions the presence of acetylcholine in the cerebrospinal fluid could hardly be demonstrated.
(2) Even during ileus no acetylcholine could be found in the cerebrospinal fluid like under normal conditions.
(3) The maximum value of cholinesterase activity in the cerebrospinal fluid under normal conditions was 38.6 CO₂ mm³/1.0 ml/30 min. The minimum 29.7 CO₂ mm³/1.0 ml/30 min. with an average of 34.7 CO₂ mm³/1.0 ml/30 min.
(4) During ileus the activity values of cholinesterase in the cerebrospinal fluid decrease according to its course, reaching the rate of -57.3% at the time of death.
II. (1) The acetylcholine content is difficult to be demonstrated under normal conditions in the blood of neither carotid artery nor jugular vein.
(2) On the contrary, during ileus, quite in contrast to normal conditions, the content of acetylcholine is greatly increased according to its course in the blood of both carotid artery and jugular vein. In the former, the increased values amounted to 0.5 γ/ml at 3 hours, 0.9 γ/ml at 6 hours, 6.5 γ/ml at 9 hours, 9.0 γ/ml at 12 hours and 8.8 γ/ml at 9 hours, 9.0 γ/ml at 12 hours and 8.8 γ/ml at 15 hours after the establish ment of ileus. On the other hand, the increased values found in the blood of jugular vein were 1.0 γ/ml at 3 hours, 5.0 γ/ml at 6 hours, 7.5 γ/ml at 9 hours, 9.2 γ/ml at 12 hours and 8.8 γ/ml at 15 hours after the establishment of ileus.
Upon comparison of the increased values of acetylcholine in the blood of both vessels, it was ascertained that the amount in the jugular venous blood was almost twice that of the carotid arterial blood at 3 hours, while at 6 hours after the establishment of ileus the increase amounted to as much as five times. Even at 9 and 12 hours the difference was evident, and at 15 hours the levels of the two approached each other . This new finding is considered to be entirely new and indicates that acetylcholine present in the central nervous tissues of the brain is clearly supplied by way of the jugular vein.
Summarizing the above results, the author states that the mechanism underlying the decrease of acetylcholine contained in the central nervous tissues of the brain and spinal cord during ileus has, at least in part, been explained by comparative analyses of the changes concerned in cholinesterase, a decomposing enzyme of acetylcholine, and in choline acetylase, a ferment in its synthesis, in conjunction with the fluctuations of the acetylcholin contents of both carotid artery and jugular vein. (Author's abstract)

---

---

To read the PDF file you will need Adobe Reader installed on your computer.