J.Jpn. Surg. Soc.. 60(3): 449-473, 1959

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STUDIES ON ACETYLCHOLINE, CHOLINESTERASE AND CHOLINE ACETYLASE IN THE INTESTINAL TISSUES DURING ILEUS

As a phase of research on the cause of death due to ileus in the Matsukura Department of Surgery, the author has investigated the behavior of acetylcholine in the enteric tissue as well as in the blood, together with that of its decomposing enzyme, cholinesterase, and its synthesizing enzyme, choline acetylase. The results obtained are as follows:
I. (1) The acetylcholine content of the enteric tissue under normal condition shows the highest value in the upper portion of the intestine with the maximum of 4.4 γ/g and the minimum of 2.2 γ/g, the average being 3.4 γ/g. The middle portion gives the maximum of 3.5 γ/g and the minimum of 1.8 γ/g, the average being 2.55 γ/g, while in the lower portion the maximum was 1.8 γ/g and the minimum 0.9 γ/g, with the average value of 1.41 γ/g. The large intestine shows the maximum of 1.1 γ/g and the minimum of 0.6 γ/g with the average of 0.76 γ/g, which is the lowest value observed.
It is thus clear that, while under normal conditions the acetylcholine content of the enteric tissue shows the lowest ualue in the large intestine, it gives the highest value in the small intestine, the value increasing as the upper end is approached.
(2) Under normal conditions, in the intestinal tissue, particularly the upper portion, the acetylcholine content is much higher than that of the thalamus which contains the greatest amount of all the central nervous tissues (the maximum being 3.2 γ/g and the minimum 2.3 γ/g, with the average of 2.75 γ/g), or that of the lumbar cord (the maximum being 3.0 γ/g and the minimum 2.4 γ/g, with the average of 2.80 γ/g).
(3) However, during the period of ileus, the acetylcholine content of the intestinal tissue tends to decrease slightly in the portion above the point of obstruction with the progress of the condition. During the terminal stage of ileus, the rate of decrease is only- 16.1% in the average, but the decrease becomes remarkable in the closed loop and in the portion below the point of obstruction. In the closed loop it disappears completely within 12 hours after the establishment of ileus, while in the portion below the point of obstruction the decrease rate is as great as -53.3% toward the terminal stage.
Thus, it is clear that during the period of ileus the acetylcholine centent of the enteric tissue, particularly the portion above the point of obstruction shows only a slight decrease, but it is remarkably reduced in the portion below and in the closed loop.
II (1) The activity of cholinesterase in the enteric tissue under normal conditions shows high values in the upper portion of the small intestine (the maximum being 104.1 CO₂ mm³/0.1g/30 M, the minimum 37.8 CO₂ mm³/0.1g/30 M, the average 66.12 CO₂ mm³/0.1g/30 M), it the middle portion (the moximum 103.4 CO₂ mm³/0.1g/30 M, the minimum 45.5 CO₂ mm³/0.1g/30 M, the average 67.17 CO₂ mm³/0.1g/30 M) and the lower portion (the maximum 103.9 CO₂ mm³/0.1g/30 M, the minimum 41.5 CO₂ mm³/0.1g/30 M, the average 65.32 CO₂ mm³/0.1g/30 M). Thus, the values are almost identical in the upper, middle and lower portions of the intestine. On the contrary, the large intestine gives the maximum of 48.2 CO₂ mm³/0.1g/30 M, the minimum of 23.9 CO₂ mm³/0.1g/30 M, the average 34.24 CO₂ mm³/0.1g/30 M, thus the values are much smaller than those of the small intestine.
(2) However, upon the institution of ileus, the value of cholinesterase activity in the portion above the point of obstruction tends to decrease slightly with the lapse of time, the terminal decrease amounting only to-8.23%. At the portion of as well as below the point of obstruction, the decrease is more remarkable and the rate of decrease in activity during the terminal stage of ileus gives the average of -35.70% and -19.19%.
These findings indicate that, while the activity of cholinesterase in the enteric tissue during ileus tends to decrease only slightly in the portion above the point of obstruction, it continues to decrease gradually at the point of obstruction and in the portion below.
III. (1) Under normal conditions the activity of choline acetylase in the enteric tissue shows the highest average value of 55.44 γ/g/h, with maximum of 85.9 γ/g/h and the minimum of 40.6 γ/g/h in the upper portion of small intestine. This is followed by that of the middle portion with the average of 49.27 γ/g/h (the maximum of 62.0 γ/g/h, the minimum of 38.6 γ/g/h), while the lowest average of 39.97 γ/g/h (the maximum of 60.9 γ/g/h, the minimum of 26.3 γ/g/h) is shown by the lower portion of small intestine. The large intestine generally indicates low values, the average being 36.15 γ/g/h, with the maximum of 50.2 γ/g/h and the minimum of 24.4 γ/g/h.
These findings indicate that the normal enteric tissue reveals only small values in the activity of choline acetylase, particularly in the large intestine. However, in the small intestine the values are generally high, the activity becoming greater as the location moves upwad. This tendency resembles the behavior of acetylcholine content of various portions of the intestinal canal.
(2) On the other hand, while no fluctuations are found, during the period of ileus, in the tissue above the point of obstruction, the activity is increased in the portion below within 6 hours after the establishment of ileus, the average value being +24.03%. The values gradually decrease there after down to the average of -42.1% in the terminal stage. In the closed loop, however, the decrease is most remarkable with the lapes of time, until the values approach zero mark during the terminal stage.
IV. (1) Normally the presence of acetylcholine in the blood can hardly be demonstrated, but during the period of ileus it shows a remarkable increase in accordance with the progress of pathology. In simple ileus the value of 9.6γ/ml is demonstrated 6 hours after, and of 10.0 γ/ml 12 hours after in compound ileus.
These results indicate that in compound ileus, in contrast to simple ileus, blood acetylchiline increases rapidly within short time. This fact agrees remarkably well with the clinical experience that in compound ileus, in contrast to simple ileus, the symptoms as well as course is both severe and rapid.
(2) Blood acetylcholine in dogs with simple ileus induced by vagotomy and autonomic nerve block increases in all cases with the lapse of time. When compared with that in dogs with untreated simple ileus, in the animals with vagotomy ileus the value of 6.7 γ/ml within 60 hours, and in those with nerve block ileus the value of 5.7 γ/ml within 60 hours, clearly demonstrating inhibitory effects on the increase, are obtained.
That is to say, the increases of blood acetylcholine during ileus can be prevented by vagotomy and autonomic nerve block.
(3) In dogs with ileus induced by totle removal of the lower portion of the intestine below the point of obstruction an extremely gradual increase of blood acetylcholine as time progresses, the value at the 60 th hour after the establishment of ileus being 1.5γml, or the most remarkable suppression is noted when compared with the above mentioned three varieties. This observation indicates that the increase of blood acetylcholine during ileus can beprevented remarkably well by total removal of the intestinal canal below the point of obstruction.
To summarize the above results of investigation on the fluctuations of acetylcholine, its decomposing enzyme, cholinesterase, and its synthesizying enzyme, choline acetylase as well as the changes of blood acetylcholine, it is noted that acetylcholine present in the enteric tissue migrates into the blood during the period of ileus, and that this phenomenon may have an intimate relation with the increased value of acetylcholine in the blood during ileus.
(author's abstract)

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