The same results were obtained by using instead of the sodium citrate solution, a solution of barium chloride, sodium sulphate, fluoride, bromide, iodide, phosphate (Na3PO4), oxalate or tartrate. Local application of solutions of any of these salts produces increased peristaltic activity. Solutions of sodium chloride have a very slight action of the same character. On the other hand, the intestinal movements are equally inhibited by calcium chloride and magnesium chloride, while strontium chloride has a similar but less powerful inhibiting action.
In testing those salts with which it was necessary to use dilutions greater than m/8, the dilution was made with a neutral fluid consisting of sodium chloride and magnesium chloride. It was found that m/6 NaCl solution increased to a very slight extent the peristaltic movements. By adding to 10 c.c. m/6 NaCl, 0.5 c.c. m/6 MgCl2, a fluid was obtained which had apparently neither stimulating nor inhibiting effects. In addition to solutions made up by dilution with this neutral fluid, others were used in which the salt solutions were diluted with distilled water. Practically the same results were obtained in both cases. It was found that 1 c.c. m/320 BaCl2 solution applied locally to the intestine is sufficient to cause strong peristaltic movements in a rabbit. This quantity contains about 0.00076 gm. barium chloride. In the case of sodium citrate, the concentration must be considerably greater. No solution of this salt more dilute than m/80 is active in a rabbit. Of all the purgative salts, barium chloride is by far the most powerful. If a drop of m/8 BaCl2 be placed on the serous surface of an intestinal loop, or if a small area be moistened with this solution by means of a camel’s hair brush, the muscle beneath the moistened area will almost immediately contract so that a ring-like constriction of the intestine is formed. This often is so sharply marked that it suggests the effect produced by tying a ligature around the intestine. This constriction remains for a few moments, and then gradually moves along the loop in the direction of the normal peristalsis. If the solution be injected into the muscle of the intestine at any point with a hypodermic needle, a similar sharp constriction takes place. If also a few drops be injected directly into a branch of the superior mesenteric artery, all that part of the loop supplied by the arterial branch will contract violently. These statements are true also in the case of sodium citrate, fluoride, sulphate, etc.; the action of these salts, however, is less powerful.
It must be added here also that the actual passage of faeces may be produced within an hour by the application of the purgative salts to the serous surfaces of the intestine. This takes place most quickly with barium chloride. It is possible to observe directly through the semi-transparent walls of the intestine the rapid passage of faecal masses from one loop to another.
The intestines of the rabbit are apparently much more sensitive to the action of sodium citrate and sulphate than are those of the dog or cat. Barium chloride, on the contrary, acts with equal strength in all these animals. In a rabbit, the intestines are always set in active peristaltic movement by contact with m/8 sodium citrate solution; and even much more dilute solutions are, as a rule, effective. In a cat, however, it was found that an m/8 solution of sodium citrate has practically no effect, while a ⁵⁄₈m solution sets the intestine in active motion. In a dog also m/8 sodium citrate solution is usually ineffective. Similarly an m/8 sodium sulphate solution is inactive in a dog while an m/2 solution of the same salt starts up distinct peristalsis. In the cat and dog also the peristalsis may be inhibited by calcium or magnesium chloride, as shown in the following experiments. The intestines of a cat were exposed in the usual manner, and an m/8 solution of sodium citrate was applied to the serous surface of the loops. There was no increased movement. There were then poured on the loops a few cubic centimetres of a mixture of 5 c.c. ⁵⁄₈m sodium citrate and 5 c.c. ⁵⁄₈m CaCl2. The loops remained motionless. After waiting a considerable time (15 minutes), a ⁵⁄₈m solution of sodium citrate alone was poured on the intestine. Almost immediately they became very active; and the peristalsis continued until calcium chloride was again applied. The loops then came to a standstill. The difference in susceptibility to the action of citrate which exists between rabbits on the one hand, and dogs and cats on the other, may be in some way connected with their being herbivorous and carnivorous animals respectively.
The action of the sodium citrate, sulphate, fluoride, etc., when applied locally, may be inhibited by the administration of an approximately equal quantity of calcium or magnesium chloride of the same concentration. The counteraction of the effect of barium chloride, however, requires a much greater concentration of calcium. Using equal quantities of the two salts, the action of the barium is usually not inhibited, a fact which I have previously stated. With greater concentrations of the calcium chloride, the antagonistic action, however, is clear. This is shown in the following experiment: Applied locally to the intestine of a rabbit 1 c.c. m/320 BaCl2 solution caused active peristaltic movements. The application of 1 c.c. m/320 CaCl2 solution exercised no inhibiting effect whatever. The same quantity of m/40 CaCl2 was then poured on the loops, and a slight but distinct quieting of the loops took place. The addition of 1 c.c. m/6 CaCl2 caused the loops to become entirely motionless. After waiting a considerable time, 1 c.c. m/8 BaCl2 was poured on the intestine. Immediately violent peristaltic movements took place. Several c.c. m/6 CaCl2 exercised practically no inhibiting influence; while 2 c.c. ⁵⁄₈m CaCl2 solution suppressed the movements entirely for a short time.
The question concerning the exact seat of action of the purgative salts remains still unanswered. Whether, upon being absorbed into the blood, they act on the central nervous system is not known. There is no evidence to show that this is the case. It seems certain, on the other hand, from the experiments here described, that they undoubtedly have a peripheral action either on the peripheral nervous mechanism or on the muscle cells themselves. It is impossible to prove that there is no action on the central nervous system, and at present it seems impossible to prove whether the peripheral action is directly on the nerves or on the muscles. The existence in the walls of the intestine of the ganglionic plexuses of Auerbach and Meissner must be taken into consideration; and with the methods available there seems to be no way of distinguishing the action on these plexuses and the direct action on the muscle cells. The ultimate effect is on the muscles and glands; and the fact that an entirely local ring-shaped constriction can be brought about by the local application of a drop of one of the salt solutions to the surface of the intestine would seem to indicate that only a small group of the circular muscle fibres themselves is affected. The fact that the nerve plexuses form a continuous network, and are intimately related in their various parts, would suggest that the occurrence of an action on these plexuses confined to so small an area is improbable. The discussion of the exact location of the action is, however, of relatively little importance, as compared with the main facts shown by these experiments, namely, that it is possible to produce, by the local application of a purgative salt to the serous surface of the intestine, a striking increase in peristalsis, and to suppress these movements by a similar application of solutions of calcium, magnesium, or strontium chloride.
These experiments also seem to decide the question as to whether the salt solutions act after being absorbed into the blood or only when placed in the intestine. According to Hay[33] and others, the salt which is absorbed into the circulation has no effect and the only action is produced by that which remains in the intestine. This is obviously not true since the solutions act much more rapidly and more powerfully when applied to the outside of the intestine, i.e., to the peritoneal surface. No action is observed until after an interval of 10 to 15 minutes after the salt solution is placed in the lumen of the intestine, while application of the same solution to the peritoneal surface causes movements of the intestine within one minute.
FOOTNOTES:
[31] Pohl (Arch. f. exp. Path. u. Pharm., Bd. 34, S. 87) stated that all sodium and ammonium salts increased the peristalsis when applied to the peritoneal surface of the intestine.
[32] MacCallum, J. B.: Amer. Journ. Physiol., Vol. X, No. V, 1904, p. 259.