The functional significance of the presence of opioid peptides in enzymatic digestion of food proteins remains uncertain. The effect of natural beta-casomorphins (beta-CMs), beta-CM-5 and beta-CM-4-NH2 (morphiceptine), and the analogue beta-[D-Ala2,4,Tyr5]CM-5-NH2 were studied in isolated rabbit ileum mounted in Ussing chambers. All three peptides caused a naloxone-reversible reduction in short-circuit current (Isc) after addition at a concentration of 10(-4) M to the serosal side of the tissue. After addition to the mucosal side, only the analogue beta-[D-Ala2,4,Tyr5]CM-5-NH2 reduced Isc. Natural beta-CMs were degraded by the intestinal mucosa, and no intact transepithelial passage was detected for these peptides, whereas beta-[D-Ala2,4,Tyr5]CM-5-NH2 was demonstrated to cross the epithelium intact when added at a concentration of 10(-3) M in the mucosal reservoir (mucosal-to-serosal flux = 3.5 +/- 1.2 nmol.h-1.cm-2). These results show that both natural beta-CMs and the protected analogue have an opiate activity on intestinal electrolyte transport. Their action from the luminal side of the intestine seems to depend on the transfer of the intact peptides from the luminal to the blood side of the tissue where opiate receptors are located. This action is prevented by luminal hydrolysis of the natural peptides.

SUMMARY Intubation techniques and scintigraphic studies were used to determine the origin and mechanism of diarrhoea in a patient with medullary thyroid carcinoma, high plasma immunoreactive calcitonin and normal circulating serotonin, substance P and prostaglandins E2 and F2,l.Normal function of the small intestine was found for the following: (a) absorption tests; (b) water and electrolyte absorption in the proximal jejunum; (c) 24 hour flow rate and composition of fluid entering the colon and (d) gastric emptying rate and small intestinal progression of a normal meal. By contrast, colonic function was markedly impaired in three ways: (a) water absorption was decreased by half; (b) as the main excreted solutes were organic acids, a large electrolyte gap was recorded in faecal water, and (c) colonic transit time of the meal marker was very short, and was in agreement with the rapid transit of ingested radioopaque markers. These data strongly suggest that decreased absorption in the colon secondary to a motor disturbance is the main mechanism of diarrhoea in this case of medullary thyroid carcinoma, while calcitonin induced small intestinal fluid secretion suggested earlier is either non-existent, or only of minor importance. whether or not diarrhoea is present, and its plasma concentration does not seem to correlate with intestinal dysfunction.4We report here a pathophysiological study of the increased faecal fluid losses in a case of MTC with diarrhoea and hypercalcitoninaemia. The results do not support the presence of a secretory mechanism, but strongly suggest that diarrhoea was the result of dysfunction of the colon caused by a marked shortening of the transit time of the intraluminal contents. Case historyA 41 year old man was admitted to hospital for chronic diarrhoea which had lasted for eight years. He passed six to 15 watery stools per day; motions were urgent and mainly postcibal, and the faeces 537 on 11 May 2018 by guest. Protected by copyright.

SUMMARY Proctocolectomy with ileal pouch anastomosis could modify motility of the small intestine through two mechanisms: obstruction or bacterial overgrowth. Motility of the jejunum was measured in 11 patients with ileoanal anastomosis six (n=6), or 12 (n=5) months after closure of the loop ileostomy. Manometric recording from the jejunum were made during fasting (four hours) and after a liquid meal (one hour). These findings were compared with those of six healthy volunteers. Motor events were classified as follows: migrating motor complex (MMC), propagated contractions, or discrete clustered contractions. All patients were investigated for bacterial overgrowth (D-glucose breath test). Only two patients had bacterial overgrowth. The frequency of MMC remained unchanged after ileo-anal anastomosis (2-83 (0*37)/four hours) compared with normal volunteers (2 81 (O*29)/four hours). During fasting, four patients had numerous propagated contractions in the jejunum. This condition was associated in two with bacterial overgrowth and in two with intubation of the reservoir. Discrete clustered contractions were found in the seven patients studied postprandially (7-6 (2-5)/h), but not in volunteers. These seven patients emptied their pouch spontaneously and bacterial overgrowth was found in only one. As this motility pattern was previously described in partial small intestinal obstruction, it is postulated that discrete clustered contractions could be the consequence of a functional obstruction as a result of anastomosis of the small intestine to the high pressure zone of the anal sphincters.Proctocolectomy with ileal pouch anastomosis is used in chronic ulcerative colitis or familial polyposis.' This procedure avoids a permanent ileostomy and combines the advantages of diseased mucosa extirpation and of continence conservation. Some patients, however, complain of excessive stool frequency, soiling, diarrhoea, and urgency, which are possibly related to modifications of small intestinal motility. In theory, ileal pouch anastomosis could modify

beta-Casomorphins (beta-CM) represent opioid peptides derived from bovine beta-casein. As opiates are known to decrease short-circuit current (Isc) and stimulate intestinal electrolyte absorption, we tested the effects of natural beta-CM-4-OH, beta-CM-5-OH, and three related analogues on electrolyte transport in rabbit ileum in vitro. At concentrations of 10(-7) to 10(-3) M, the three analogues (beta-[D-Ala2]CM-4-NH2, beta-[D-Ala2,Met5]CM-5-NH2, and beta-[D-Ala2,4,Tyr5]CM-5-NH2) caused a dose-dependent, naloxone-reversible reduction in Isc after addition to the serosal side of the preparation. beta-[D-Ala2,4,Tyr5]CM-5-NH2 also decreased Isc after mucosal addition. Serosal addition of the same analogue stimulated absorption of sodium and chloride (+2.90 +/- 0.95 and +2.12 +/- 0.60 mu eq . h-1 . cm-2, respectively) and inhibited residual flux (-1.80 +/- 0.57 mu eq . h-1 . cm-2). The natural beta-CM tested did not decrease Isc. These results demonstrate that beta-CM analogues stimulate intestinal absorption of electrolytes by an opioid mechanism. The fact that beta-[D-Ala2,4,Tyr5]CM-5-NH2 was effective on the mucosal side favored the hypothesis that certain food-related opioid peptides might be absorbed by the intestine.

Summary. 8-casomorphins (, Introduction.