A somewhat larger quantity of the cascara solution injected subcutaneously produces increased peristaltic activity after an interval of several minutes.
If the cascara solution be applied directly to the serous surfaces of the intestine, very strong contractions and peristaltic movements result in 2 or 3 minutes. A solution of m/25 NaHCO3 alone produces very slight movements when applied in this way. These can, however, be readily distinguished from those produced by cascara. The latter are much more powerful, are slower in developing, and can be only partially inhibited by m/6 CaCl2. The movements following the application of pure NaHCO3 solution, however, are weak, they appear almost immediately, and can be entirely suppressed by the application of m/6 CaCl2 solution.
When the cascara solution is placed in the stomach no movements appear in the intestine even after 15-30 minutes. The acid of the gastric juice has evidently precipitated the cascara, which cannot act until it is passed on into the intestine where it may be dissolved in the alkaline juice of the intestine. If instead of placing the solution in the stomach it is injected directly into the small intestine, increased peristaltic movements begin within 5 minutes. Here it evidently remains in solution and is absorbed. It is for this reason that in human beings cascara taken by mouth acts only after several hours. It is precipitated in the stomach and must reach the intestine before it is dissolved and absorbed.
In addition to the increased peristaltic activity caused by the cascara, there seems to be also an increase in the secretion of fluid into the lumen. One or two hours after the injection 20-30 c.c. fluid could be collected from the small intestine. Without the purgative it is rarely possible to obtain more than 5 to 10 c.c.
It was found that calcium chloride has only a very transient effect in inhibiting the increased movements produced by cascara. For 2 or 3 minutes following the injection of CaCl2 the movements were usually quieted, but they rapidly began again and continued as vigorously as before.
The behavior of rhubarb is in every way similar to that of cascara. It is less readily soluble, but the solution acts in a way quite like that described for cascara.
It is further well known that aloin injected subcutaneously causes increased peristalsis. A study has recently been made of certain constituents of the derivatives of the aloes group of purgatives. Esselmont,[93] following the work of Tschirch,[94] experimented with a number of substances obtained from these purgatives. Aloëemodin is present not only in aloes, but also in Cascara sagrada and senna leaves. A small amount of this substance acts as a purgative. Alochrysin, aloingrin, barbaloin, all act as purgatives. Chrysophanic acid, which is found in aloes, rhubarb, and senna is a mild purgative. It is of interest to note that each of these substances is either a di-or tri-oxymethylanthrachinon. They owe their purgative action, according to Tschirch, to their containing the oxymethylanthrachinon group.
Some experiments[95] which I recently made on a jellyfish (Polyorchis) with some of the vegetable purgatives are of interest. They were suggested by the experiments of Loeb[96] on the effect of various salts on the isolated center of the animal and of a related form (Gonionemus). When separated from the margins the bell-like centers of these jellyfish do not beat in pure sea-water. In case of Gonionemus it was found that the addition of one of a number of salts (calcium precipitants) caused the center to beat. This group of salts includes the so-called saline purgatives.
The methods used in the experiments with vegetable purgatives were practically the same as those used by Loeb. The animal was bisected just above the ring of sense organs in order to entirely remove the margin containing the main nervous system. The center was then placed in mixtures of sea-water and solutions of the purgatives. The center never beats in pure sea-water, but was found to beat vigorously in sea-water to which a small quantity of a solution of cascara, rhubarb, aloin, podophyllin, or colocynth had been added. It was necessary to dissolve the cascara and rhubarb extracts in m/24 NaHCO3, since they are not soluble in pure water. The centers do not beat in sea-water to which pure m/24 NaHCO3 has been added in quantities equivalent to those added with the purgative solution.
A solution of ¹⁄₄ g. cascara extract was made in 50 c.c. m/24 NaHCO3. It was found that a mixture of 25 c.c. sea-water + 2 c.c. of this cascara solution was the most favorable for producing rhythmical contractions in the isolated center of Polyorchis. Contractions lasted 10-15 minutes.