Histologically the pyloric glands and the glands of Brunner in the. Ivy(7) and his co-workers seem to believe, at the present time, in the

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1 6I2.323[6I2.33 6I2.OI5.2I THE SMALL INTESTINE AND GASTRIC SECRETION. (With special reference to Brunner's Glands.) BY MARGARET M. MURRAY. (From the Department of Physiology, Bedford College.) EVIDENCE has repeatedly been advanced that the activity of extracts of the pyloric mucous membrane in causing gastric secretion is also exhibited by those of the small intestine. The present investigation was directed towards elucidating the presence of any structure which might be indicated as concerned in the intestinal phase. Edkins and Tweedy(l) definitely stated that the duodenal mucous membrane also, though to a lesser degree, acted as the pyloric mucous membrane does. K eeton and Ko ch believe that a specific hormone is produced in the upper small intestine as well as in the stomach. Babkin(3) in his book points out that although the pylorus and the part of the duodenum in which Brunner's glands are found belong anatomically to different parts of the alimentary canal, they are related functionally, and suggests that this is by reason, possibly, of the similarity of their secretions. Histologically the pyloric glands and the glands of Brunner in the duodenum show close resemblances. This might suggest that they have some function in common. Pavlov recognized (4) that gastric secretion could be excited from the intestine. Lim (5) set out to investigate the distribution of "gastrin" in the stomach and duodenum with a view to localizing the cells responsible for its production. He found that extracts both of the pyloric region and of the duodenum were effective in producing gastric secretion when injected into the blood; other parts of the small intestine were practically without effect. In his conclusions he considered it not unlikely that the common source of the excitant was the mucoid type of cell which occurs in both regions. Later Ivy, L im, and McCarthy(6) stated that "an intestinal phase is proven." Ivy(7) and his co-workers seem to believe, at the present time, in the presence of a gastric stimulant in the blood, and that this can be produced by contact of HCI with the duodenum, and that in duodenal

2 SMALL INTESTINE AND GASTRIC SECRETION. washings "gastrin" exists. Walawski s) found duodenal extracts more effective in producing gastric secretion when injected subcutaneously than those of jejunum or ileum. The object of the present work, then, was to investigate the "intestinal phase" of gastric secretion, and more particularly to determine whether the active part of the duodenum is restricted to that in which Brunner's glands are found, by comparing the response of the fundus of the stomach to intravenous injection of extracts of duodenum in which Brunner's glands were present with that obtained when they were absent. Method of preparation of extracts. Extracts of different regions of the duodenum were made by the method of Dalmau(9). Small portions of the mucous membrane and the submucous coat were ground with sand and ten times their weight of N/1 HCI. The extract was then boiled for 3 minutes, cooled, nearly neutralized by cautious addition of N/2 NaOH, then filtered. The filtrate was added to nine volumes of acetone. The precipitate so produced was filtered off, washed with ether, and dried. The powder was ground with 15 c.c. Ringer's solution, filtered again, and the filtrate used for intravenous injection. In the first two experiments pig's duodenum was used. Pieces were taken for extraction and for histological examination, so that the results might be correlated. In the pig Brunner's glands go surprisinglyfar down the duodenum (about 2 cm.). Later, cat's duodenum was used. In the cat there is only a very small region of duodenum containing B runner's glands. 2 cm. from the pylorus is the absolute limit of these glands. This gave only about 3 g. of tissue for extraction, so that only small quantities of the solutions were available for injection. Other parts of the duodenum were taken for comparison. The extracts in any one experiment were made from equal weights of the mucous membrane employed. The extracts were numbered in order from the pylorus downward. The injections were intravenous. It has been shown by Gutowski(1o) that histamine given intravenously in cats causes practically no response; I have been able to confirm this, so the histamine effect if present at all must have been small. Method of experiment. All the experiments were done on cats, and were of the acute type. The animals were fed on milk for the last few days before the experiment. PH. LXIX. 4 49

3 5 M. M. MURRAY They were ansesthetized with ether, placed in a warm saline bath, decerebrated, and then allowed a period of half an hour to get over the main effect of the anaesthetic. The oesophagus was tied so as to occlude it and crush the vagi, and a tube was tied into the pylorus. The stomach was washed out till the contents were clean and acid free. In all the experiments recorded even the first washings were clean. Into the stomach there were introduced 25 c.c. saline; such a volume as could not cause secretion by distension. Then at intervals of 1 minutes three injections, each of 2 c.c. of one of the extracts were made into the external jugular vein. After half an hour (from the last injection) the liquid from the stomach was withdrawn, the stomach washed out and allowed a period of rest before repeating this procedure with another extract for comparison. The potency of the extract was determined by testing the liquid from the stomach with Gunsberg's reagent and then estimating the HCI in a known volume of the liquid after boiling for 3 minutes, by titration with N/5 NaOH, using methyl orange as indicator. The pepsin in the liquid from the stomach was estimated by Fuld's edestin method and the results are given in Fuld's units. The order in which the extracts were used was varied in different experiments so as to exclude the factor of fatigue and delayed effect. A typical series of experiments is given in the table on p. 51. A consideration of these figures shows that more HCI and more pepsin were secreted when the extracts injected were made from parts in which Brunner's glands were found to be present than when made from parts in which they. were not. Ten experiments are cited and this result is unambiguous in all but one (No. 12). In this one experiment an extract from a part containing no Brunner's glands evoked a secretion containing definitely more pepsin, though also definitely less acid. In three (Nos. 14, 16 and 18) the differences in the amount of HCI secreted were small, but in them the differences in pepsin were clear enough in support of the general inference drawn from the whole series. In most of the experiments the actual secretions appear to be small. This is no doubt due to several factors; cats do not give, under these conditions, large secretions; and again, it must be remembered that the extent of Brunner's glands, and hence the weight of tissue used in the extractions, was small. Of course it must be realized that the tissues extracted were unavoidably heterogeneous, but it would seem reasonable to assume that whatever secretagogues or vaso-dilators were present in one part of the duodenum would be present in another close to it, so that in the parts

4 SMALL INTESTINE AND GASTRIC SECRETION. 51 Exp. 1 Extra 11 * I!ature of extract ct by acetone method (3) from Ipig's duodenum. Numbers in ord.er from pylorus (4) pig's (3) cat's,,,, VP VP,,S,,,,,,,, pi, VP,, i,,,,, " pyloric Brunner's5 glands, determined histologically HCI in mg. Pepsin secreted by Fuld * The cat from which the extracts were made had previously been used for one of the experiments. selected for extraction differences of activity if any would depend upon the presence or absence of Brunner's glands. The contrast therefore in the results obtained with extracts of the two different parts must appear to be due to something specific in Brunner's glands capable of causing an undelayed excitation of gastric secretion on intravenous injection. When Brunner's glands were not present in the intestinal mucous membrane extracted very little secretion was obtained. SUMMARY. 1. The response of the gastric mucosa to intravenous injections of extracts of different parts of the duodenum has been investigated. 2. The results show that when that part of the duodenum which contains Brunner's glands is used, the secretion by the stomach is greater, more HCO and pepsin being produced. When parts that do not contain Brunner's glands are used the effect is insignificant in almost every case. 4-2

5 52 M. M. MURRAY. I have to record my thanks to Dr Nora Edkins for maling the histological observations, and to Prof. E dkins for suggestions. REFERENCES. 1. Edkins and Tweedy. This Joum. 38. p Keeton and Koch. Amer. J. Physiol. 37. p Babkin. Die aussere Sekretion der Verdauungsdriisen, p Pavlov. The Work of the Digestive Glands Lim. Quart. J. Exp. Physiol. 13. p Ivy, Lim and McCarthy. Ibid. 15. p Ivy and Farrell. Amer. J. Physiol. 74. p Walawski. C. R. Soc. Biol. Paris, 98. p Dalmau, M. Treb. de la Soc. Biol. Barcelona, 19. p Gutowski. C. R. Soc. Biol. Paris, 91. p