The intravenous infusion of bombesin produced in intact dogs and, more strikingly in dogs provided with gastric fistulae a sharp increase in plasma levels of immunoreactive gastrin and at the same time a stimulation of gastric acid secretion. Gastrin response was correlated with the dose of bombesin from approximately 0.1 μg kg−1 h−1 (threshold) to 1 μg kg−1 h−1 (maximum gastrin release). Atropine and metiamide reduced or inhibited gastric acid secretion stimulated by bombesin, but did not affect the rise in gastrin levels. Acidification of the whole stomach or of a perfused antral pouch caused a reduced or delayed response to bombesin. However, the inhibitory effect of acidification could be surmounted by prolonging the duration of bombesin infusion. Antrectomy greatly reduced the rise in gastrin levels and the increase in acid gastric secretion produced by bombesin, but left unaffected the gastric secretagogue effect of pentagastrin. It is concluded that bombesin is a potent releaser of gastrin from the antral mucosa. The possible influence of the renal effects evoked by bombesin in the dog on the gastrin response to the polypeptide is discussed.

In conscious rats, histamine given intraperitoneally produced a delay in gastric emptying. A dose-dependent relationship was observed. The threshold dose was about 1 mg/kg, the calculated maximum dose 35 mg/kg. The inhibitory effect of histamine on gastric emptying was abolished by pretreatment with H₁-receptor antagonists and mimicked by 2-aminoethylthiazole; on the contrary, an H₂-receptor agonist (dimaprit) and H₂ antagonists were completely ineffective. This suggested that receptors involved in delay of gastric emptying are of the H₁ type. The inhibitory effect of histamine on gastric emptying was not modified by pretreatment with the well-known inhibitors of gastric secretion, metiamide and cimetidine. This is consistent with the idea that the delay in gastric emptying observed with histamine may not be related to the gastric secretory properties of this compound.

It is generally accepted that the gastro-intestinal mucosa represents the most important site of production and storage of 5-hydroxytryptamine (5-HT) in mammals. In the rat, the total 5-HT in the gastro-intestinal tract may vary according to age, weight, strain, diet, and probably season, between 80 (Erspamer, 1954) and 300 ,ug/kg (Bertaccini, unpublished).Of this total amount, about 8-15 % is contained in the stomach, 30-40 % in the small intestine and the remaining 45-60 % in the large intestine.On the basis of these data and the easy availability of a large number of uniform animals, rats seemed particularly suitable for studying the effect of removal of important portions of the 5-HT-secreting intestinal tissue or of the entire gastro-intestinal tract, on the serum and tissue levels of 5-HT as well as on the urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT. METHODSExperimental animals. The large intestines were removed from three groups of rats (300 in all) weighing 180-250 g. Each group consisted of aniimals of the same breed and sex, and of approxiimately the same age. The first experiment was carried out on male rats kept on a non-standard laboratory diet; the second on female rats, and the last on male Wistar rats. In the second and third experiments the rats were kept on the Rockland diet. Complete gastro-enterectomy was performed on 60 rats of both sexes; 30 rats were kept as controls.Operation procedure and post-operative treatment Removal of the large inte8tine. The rats were starved 24 hr before operation, but were allowed water ad lib.The well known resistance ofrat's peritoneal cavity against infections allowed the operation to be performed with care for cleanliness but without rigorous asepsis. The operative area was shaved and painted with 5 % tincture of iodine U.S.P.; penicillin 10,000 u./rat was given subeutaneously for 1 day before and 2 days after the operation, to reduce the risk of peritonitis due to leakage at the site of anastomosis.Under light ether anaesthesia the abdomen was opened by a mid-line incision and the appendix was delivered from the peritoneal cavity on to saline packs. Beginning from the ileocaecal valve, all the blood vessels supplying the portion of the intestinal tract that was to

No abstract

1. In the intact conscious dog, caerulein causes emesis and evacuation of the bowel. The mean effective dose by the intravenous route is 0.4-0.5 jig/kg, and by the subcutaneous route 3-4 jg/kg. 2. The gall bladder in situ or as an isolated preparation is highly sensitive to caerulein. A few ng/kg injected intravenously are sufficient to stimulate the gall bladder in situ and less than 1 ng/kg per min is effective when infused intravenously. The isolated gall bladder is contracted by caerulein in concentrations as low as 0.03-2 ng/ml. Krebs solution. There is no tachyphylaxis but, generally, a good dose-response relationship. Hence the gall bladder, especially that of the guinea-pig, appears to be very suitable for the bioassay of caerulein and related peptides. 3. In situ, the musculature of the gastrointestinal tract is also highly sensitive to caerulein. Doses as low as 1-5 ng/kg, administered intravenously, have a spasmogenic action on jejunal loops of the dog, and slightly larger doses contract the small intestine of the cat. The stomach and the large intestine seem to be somewhat less sensitive to the polypeptide. Caerulein has a considerable spasmogenic action on the rat pylorus but relaxes the sphincter of Oddi of the guinea-pig. 4. Isolated preparations of the gastrointestinal tract are relatively insensitive to caerulein and tachyphylaxis occurs readily.5. Blockade with atropine produces different effects in different intestinal segments and in different animal species. The spasmogenic action of caerulein on the gall bladder is atropine-resistant. 6. The effects of caerulein are -similar to those of cholecystokininpancreozymin in the organs tested in situ or as isolated preparations. Caerulein, however, is always more potent than cholecystokinin-pancreozymin, even on a molar basis. Compared with caerulein, human gastrin I has negligible activity. 7. The possible use of caerulein in cholecystography is discussed.In a preceding paper the actions of caerulein on the systemic arterial blood pressure of some common laboratory animals were reported