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The tachykinins eledoisin and physalaemin, as well as the bombesin peptides litorin, ranatensin and bombesin itself, exert in the pigeon a powerful dipsogenic effect which is similar, as far as drinking behaviour, time course and dose-response relationship are concerned, to that evoked by angiotensin II (Ang II)1–5.

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 mug/kg, and by the subcutaneous route 3-4 mug/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 cholecystokinin-pancreozymin 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.

Caerulein, the active decapeptide which has been detected in our Laboratory in extracts of the skin of the Australian frog Hyla caerulea, is certainly one of the most versatile polypeptides we know so far. In fact, it displays a number of striking pharmacological actions.

L'infusione di ceruleina (2 ng/kg/min) produce nel cane un significativo aumento della concentrazione del glucagone, oltre che della insulina, nella vena pancreatico-duodenale superiore, senza significative modificazioni della glicemia.

Vengono riportate le proprieta di una serie di peptidi sintetici affini per struttura alla fisalemina.

The study of some biologically vasoactive substances has suggested the possibility of additional research work and clinical applications.

Summary 1 . Insulin concentration changes in pancreatico-duodenal venous plasma were studied in anaesthetized dogs injected with caerulein. 2 . Rises in insulin concentration were elicited by rapid intravenous injection of caerulein, as well as by intravenous infusion. Threshold doses were 10 ng/kg and 0·5–1 (ng/kg)/min respectively. 3 . At the highest dose used (500 ng/kg by rapid intravenous injection and (25 ng/kg)/min by intravenous infusion) the increase in immuno-reactive insulin release was approximately 7 to 9 times the base levels. 4 . Adrenalectomy potentiated the effects of intravenous infusion of caerulein. 5 . On a molar basis, caerulein was 2–3 times as active as pancreozymin. 6 . It is concluded that caerulein is a potent stimulant of pancreatic islets in the dog and that it may be considered as a model peptide, capable of being substituted for pancreozymin in any experiment. 7 . The mechanism of the insulin stimulating effect of caerulein is discussed. The possibility of a direct “β-cytotropic” effect of the peptide is suggested.

The present communication gives an account of the isolation, structure and pharmacological properties of the caerulein-like polypeptide occurring in the skin of Phyllomedusa sauvagei from north-western regions of Argentina. For the new polypeptide, a nonapeptide closely resembling caerulein both from a biological and chemical point of view, the name phyllocaerulein is proposed. This paper also describes the occurrence of phyllocaerulein or related peptides in the skin of other Phyllomedusa species. A complete description of methods used in the isolation of phyllocaerulein as well as in the determination of amino-acid composition and amino-acid sequence of the polypeptide may be found in a preceding paper dealing with the isolation and the amino acid sequence of caerulein (Anastasi, Erspamer & Endean, 1968 ; Anastasi, 1969)., Material digitalizado en SEDICI gracias a la colaboración del Dr. Jorge Williams (FCNM-UNLP)., Facultad de Ciencias Naturales y Museo

1. Caerulein displayed a potent stimulant action on pancreatic secretion in the dog. Threshold doses were 1-5 ng/kg by rapid intravenous injection, 0.25-1 ng/kg per min by intravenous infusion and 50-100 ng/kg by subcutaneous injection. There was a conspicuous increase not only in the volume flow of pancreatic juice but also in the output of solid constituents of the juice and of amylase. However, continuous stimulation of pancreatic secretion by intravenous infusion of caerulein resulted in a progressive reduction of the amylase concentration and still more of the dry residue content of pancreatic juice. The bicarbonate concentration in pancreatic juice produced by caerulein was similar to that observed in juice secreted following pancreozymin administration or following other stimuli causing the same rate of flow of pancreatic juice.2. On a molar basis, caerulein was 25-30 times as active as human gastrin I and 3-6 times as active as cholecystokinin-pancreozymin. The presence in the molecule of caerulein of a sulphated tyrosyl residue at position 4 of the decapeptide (position 7 starting from the C-terminus) was a necessary prerequisite for the manifestation of the cholecystokinin-pancreozymin-like actions of caerulein. The C-terminal heptapeptide of caerulein retained much of the activity of the intact caerulein molecule.3. At high dose levels (50-200 ng/kg in the dog, 1 mug/kg in the rat, by rapid intravenous injection) caerulein stimulated the flow of hepatic bile in the dog and the rat. The dry residue of the bile and the cholesterol concentration were appreciably greater in rats treated with caerulein than in control rats.4. The activity spectrum of caerulein was identical with that of cholecystokinin-pancreozymin. This is readily explained on the basis of the almost identical structure of the C-terminal octapeptide of the two peptides.5. Caerulein and some caerulein-like peptides may be considered as model peptides, capable of being substituted for cholecystokinin-pancreozymin in all the possible experimental and clinical uses of the duodenal hormone, with the important advantage that they are more easily available.6. The question is raised whether cholecystokinin-pancreozymin obtained from the duodenum by acid extraction is the authentic hormone or rather a carrier polypeptide from which a smaller active peptide may be set free, when needed, into the circulation.

La caeruleina, nonapeptide attivo della pelle diHyla caerulea, possiede un insieme di potenti azioni farmacologiche sulla muscolatura liscia vasale ed extravasale e sulle secrezioni del tubo digerente. La caeruleina provoca una relativamente prolungata caduta della pressione del sangue nel cane e nel coniglio, contrae potentemente la muscolatura in situ dello stomaco, dell'intestino e soprattutto della cistifellea, stimola poderosamente la secrezione gastrica, la secrezione pancreatica e, in misura minore, la secrezione biliare. In queste sue multiformi azioni farmacologiche la caeruleina risulta piu potente rispettivamente della bradichinina, della gastrina e della colecistochinina-pancreozimina.